Search

Background: Recent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations., Objectives: We conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD., Methods: Estimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census., Results: CKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males., Conclusions: Our findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy.

Objective: Influenza causes severe morbidity and mortality. This systematic review aimed to assess the incidence, etiology, and resource usage for influenza in Latin America and the Caribbean., Design: Meta-analytic systematic review. Arcsine transformations and DerSimonian Laird random effects model were used for meta-analyses., Setting: A literature search from 1980 to 2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, Ministries of Health, PAHO, proceedings, reference lists, and consulting experts., Sample: We identified 1092 references, of which 31 were finally included, in addition to influenza surveillance reports. We also used information from the 10 reports from the collaborative group for epidemiological surveillance of influenza and other respiratory virus (GROG), and information retrieved from the WHO global flu database FLUNET., Main Outcome Measures: Incidence, percentage of influenza specimens out of the total received by influenza centers and resource-use outcomes., Results: A total of 483 130 specimens of patients with influenza were analyzed. Meta-analysis showed an annual rate of 36 080 (95%CI 28 550 43 610) influenza-like illness per 100 000 persons-years. The percentage of influenza out of total specimens received by influenza centers ranged between 4.66% and 15.42%, with type A the most prevalent, and A subtype H3 predominating. The mean length of stay at hospital due to influenza ranged between 5.8 12.9 days, total workdays lost due to influenza-like illnesses were 17 150 days, and the mean direct cost of hospitalization was US$575 per laboratory-confirmed influenza case., Conclusions: Our data show that seasonal influenza imposes a high morbidity and economic burden to the region. However, the vaccine-uptake rate has been low in this region. Population-based cohort studies are required to improve the knowledge about incidence and resource utilization, which would inform healthcare authorities for decision making., (© 2012 John Wiley & Sons Ltd.)

Background: Mexico initiated mass vaccination with the attenuated human rotavirus vaccine (Rotarix) in 2006. This postlicensure study aimed to assess any potential temporal association between vaccination and intussusception in Mexican infants., Methods: Prospective, active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010. The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis., Results: Of the 753 episodes of intussusception reported in 750 infants, 701 were in vaccinated infants (34.5% post-dose 1, 65.5% post-dose 2). The relative incidence of intussusception within 31 days of vaccination was 1.75 (95.5% confidence interval [CI]: 1.24-2.48; P=0.001) post-dose 1 and 1.06 (95.5% CI: 0.75-1.48; P=0.75) post-dose 2. The relative incidence of intussusception within 7 days of vaccination was 6.49 post-dose 1 (95.5% CI: 4.17-10.09; P<0.001) and 1.29 post-dose 2 (95.5% CI: 0.80-2.11; P=0.29). Clustering of intussusception within 7 days of vaccination was observed post-dose 1. An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated., Conclusion: This is the largest surveillance study for intussusception after rotavirus vaccination to date. A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose. It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception. This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination.

Background: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region., Methods: We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated., Results: We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin., Conclusions: Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.

Background: Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age., Methods: Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes)., Results: Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (S. pneumoniae, H. influenzae, S. pyogenes or M. catarrhalis) was cultured from 65.9% (60/91) of episodes. H. influenzae (55.5%; 35/63 episodes) and S. pneumoniae (34.9%; 22/63 episodes) were the most frequently reported bacteria. Among H. influenzae isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for H. influenzae was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six H. influenzae positive samples (66.7%) from recurrent episodes., Conclusions: We found H. influenzae and S. pneumoniae to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.

Background: Rotavirus vaccination was introduced in Panama in March 2006. This study was carried out in order to describe the trends in gastroenteritis-related (GER) hospitalizations and mortality in children <5 years of age during the pre- and post-vaccination periods., Methods: Data from the Expanded Program on Immunization (Ministry of Health) were used to calculate vaccine coverage. GER mortality and hospitalizations were obtained through database review of the Contraloría General de la República and hospital discharge databases of five sentinel hospitals, for the period 2000-2008. Mean rates of GER mortality and mean numbers of hospitalizations during the baseline pre-vaccination period (2000-2005) were compared to those of 2007 and 2008., Results: National coverage for the second rotavirus vaccine dose increased from 30% in 2006 to 62% in 2007 and 71% in 2008, varying from 62% in the West region to 77% in the Panama region. Overall, at 2-years post-vaccine introduction, the GER mortality rate in Panama had decreased by 50% (95% confidence interval (CI) 46-54). During 2000-2005, the GER mortality rate in children (<1 year) was 73/100 000, decreasing by 45% (95% CI 40-51) in 2008. In children aged 1-4 years, the GER mortality rate was 20.3/100 000 (2000-2005), decreasing by 54% (95% CI 48-60) in 2008. The Panama region registered the highest mortality rate reduction (69%; 95% CI 58-81) for 2008. During 2008, GER hospitalizations among children <5 years of age decreased by 30% (95% CI 21-37) from the mean number of hospitalizations during 2000-2005., Conclusions: A substantial reduction in GER mortality and hospitalizations was observed following the introduction of rotavirus vaccine in Panama., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: This systematic review evaluated the incidence, etiology, and use of resources in bacterial, non-tuberculosis community-acquired pneumonia (CAP) in immune-competent children aged <5 years., Methods: Systematic searches (1980-2008) were performed using MEDLINE, Cochrane Library, EMBASE, LILACS, generic, and academic Internet searches. Regional health ministries, the Pan American Health Organization (PAHO), regional proceedings, doctoral theses, and the reference lists of included studies were also searched, and experts were consulted. Arcsine transformations and the DerSimonian-Laird random-effects model were used for proportion meta-analyses., Results: The search yielded 1220 references; 60 were included in the meta-analysis, giving a total 23 854 CAP episodes with an incidence of 919/100 000 child-years in children aged <5 years. Streptococcus pneumoniae was the most frequently isolated agent (11.08%; 95% confidence interval (CI) 7.63-15.08), and pneumococcal serotype 14 was most prevalent (33.00%; 95% CI 25.95-40.45). Other common agents were Haemophilus influenzae and Mycoplasma pneumoniae. Health economics data on CAP in the region were scarce. About one-fourth of CAP patients required hospitalization (median length of stay 11 days, range 5-13.5 days)., Conclusions: The burden of CAP was substantial, with S. pneumoniae, H. influenzae, and M. pneumoniae being the most common pathogens identified. High quality primary studies on disease incidence, use of health resources, and standardized data collection on disease burden and circulating strains are essential to provide baseline data for the future evaluation of vaccine impact., (© 2011 International Society for Infectious Diseases. All rights reserved.)

Background: Acute otitis media (AOM) is one of the most common childhood diseases requiring antimicrobial prescription in pre-school children. This systematic review aimed to estimate the AOM incidence, bacterial etiology and use of resources in children aged <6 years in Latin America and the Caribbean (LA&C)., Methods: A systematic search using keywords otitis or middle ear and inflammation was performed for articles published during 1988-2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, generic and academic internet searches, Ministries of Health, PAHO, regional proceedings, reference lists and consulting experts. Pairs of reviewers independently selected articles and assessed their methodological quality with a checklist of essential items from the STROBE statement according to pre-specified criteria. Studies involving immune-competent children with AOM were considered. Arcsine transformations were used for proportion meta-analyses., Results: Annual AOM incidence in four studies in children aged <5 years ranged from 1,171-36,000 episodes/100,000 children. Meta-analysis on etiology and pneumococcal serotypes included 18 studies and 125, 519 children with AOM from six LA&C countries. Meta-analysis per serotype showed that Streptococcus pneumoniae (32.4%; 95%CI=27.1-38.0%) and Haemophilus influenzae (26%; 95%CI=19.5-33.1%), including non-typeable H. influenzae (18.3%; 95%CI=9.5-33.1%) were the most prevalent. The most commonly observed pneumococcal serotype was 19F (24.0%; 95% CI 17.0-32.0%). Data on use of health resources were scarce., Conclusions: Streptococcus pneumoniae and H. influenzae were the most frequent AOM bacterial pathogens, consistent with the international literature from other regions. Future studies on AOM incidence and health resources usage will help better define the impact of this disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Streptococcus pneumoniae and Haemophilus influenzae have been consistently reported to be the two major bacterial pathogens responsible for acute otitis media (AOM), mainly from studies in the US and Europe. However, data on bacterial pathogens causing AOM in Latin America are limited. Understanding the relative importance of these pathogens in a specific setting, the serotype distribution, and their antibiotic susceptibility levels is important to provide local vaccine and treatment recommendations. We therefore conducted a prospective, multi-center, tympanocentesis-based epidemiological study of Mexican children three months to less than five years of age. Fifty percent of episodes were in children who had received at least one dose of PCV7. Overall, 64% of samples were culture positive for bacterial pathogens. H. influenzae and S. pneumoniae were the leading causes of bacterial AOM, detected in 34% and 29% of AOM episodes, respectively. The most commonly isolated S. pneumoniae serotypes were 19A, 19F and 23F. All H. influenzae isolates were identified as non-typeable. Seventy-four percent of S. pneumoniae were susceptible to penicillin, while 97% were susceptible to amoxicillin/clavulanate. All H. influenzae samples were susceptible to amoxicillin/clavulanate and cefotaxime, 95% to cefuroxime and 75% to ampicillin. Both S. pneumoniae and non-typable H. influenzae represent important targets for vaccination strategies to reduce AOM in Mexican children., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Brazil initiated universal immunization of infants with the G1P[8] human rotavirus (RV) vaccine in March 2006. This study evaluated vaccine effectiveness (VE) against severe rotavirus gastroenteritis (RVGE) hospitalizations., Methods: Matched case-control study conducted at 4 hospitals in Belém from May 2008 to May 2009. Cases were children hospitalized with RVGE age-eligible to have received 2 doses of the human RV vaccine (≥ 12 weeks of age and born after March 6, 2006). For each case, 1 neighborhood and 1 hospital control without gastroenteritis was selected, matching by birth date (± 8 and ± 6 weeks, respectively). Matched odds ratio of 2-dose RV vaccination in cases versus controls was used to estimate VE (1 - odds ratio × 100%)., Results: Of 538 RVGE cases, 507 hospital controls and 346 neighborhood controls included, 54%, 61%, and 74% had received both RV vaccine doses. VE against RVGE hospitalization was 75.8% (95% confidence interval [CI]: 58.1-86.0) using neighborhood controls and 40.0% (95% CI: 14.2-58.1) using hospital controls. VE in children 3 to 11 months and ≥ 12 months of age was 95.7% (95% CI: 67.8-99.4) and 65.1% (95% CI: 37.2-80.6) using neighborhood controls, and 55.6% (95% CI: 12.3-77.5) and 32.1% (95% CI: -3.7-55.5) using hospital controls. G2P[4] accounted for 82.0% of RVGE hospitalizations. G2P[4]-specific VE was 75.4% (95% CI: 56.7-86.0) using neighborhood controls and 38.9% (95% CI: 11.1-58.0) using hospital controls., Conclusions: Although fully heterotypic G2P[4] was the predominant RV strain, good VE was demonstrated. VE was highest in children aged 3 to 11 months. However, protection in children ≥ 12 months of age, important for optimal public health impact, was significantly sustained based on estimates obtained using neighborhood controls.

Objectives: Rotavirus vaccination was introduced in Brazil in March 2006, targeting an annual birth cohort of approximately 3.5 million. We analyzed trends in all-cause gastroenteritis-related deaths in children <5 years of age during the pre- and post-vaccination periods., Methods: Data from the National Immunization Program and the Mortality Information System were used to calculate vaccine coverage and mortality rates related to gastroenteritis in children <1 year and 1-4 years of age, using population estimates from the census as the denominator. Relative reductions in mortality rates were calculated for 2007 and 2008, using the 2004-2005 mean as baseline before vaccine introduction., Results: Coverage of two doses of human rotavirus vaccine was 39% in 2006, increasing to 72% in 2007 and 77% in 2008. During 2004-2005, the gastroenteritis mortality rate in children <1 year of age was 56.9 per 100 000, decreasing by 30% (95% confidence interval (CI) 19-41) in 2007 and by 39% (95% CI 29-49) in 2008. In children 1-4 years of age, the mortality rate was 4.5 per 100 000 during 2004-2005, decreasing by 29% (95% CI 10-49) in 2007 and by 33% (95% CI 15-52) in 2008., Conclusions: The decreased rates of childhood gastroenteritis-related deaths in Brazil following rotavirus vaccine introduction, particularly among children <1 year of age, suggest the potential benefit of vaccination., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Acute otitis media (AOM) is one of the most frequently encountered bacterial infections in children aged < 5 years; Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are historically identified as primary AOM causes. Nevertheless, recent data on bacterial pathogens causing AOM in Latin America are limited. This prospective study aimed to identify and characterize bacterial etiology and serotypes of AOM cases including antimicrobial susceptibility in < 5 year old Colombian children., Methods: From February 2008 to January 2009, children ≥3 months and < 5 years of age presenting with AOM and for whom a middle ear fluid (MEF) sample was available were enrolled in two medical centers in Cali, Colombia. MEF samples were collected either by tympanocentesis procedure or spontaneous otorrhea swab sampling. Bacteria were identified using standard laboratory methods, and antimicrobial resistance testing was performed based on the 2009 Clinical and Laboratory Standards Institute (CLSI) criteria. Most of the cases included in the study were sporadic in nature., Results: Of the 106 enrolled children, 99 were included in the analysis. Bacteria were cultured from 62/99 (63%) of samples with S. pneumoniae, H. influenzae, or S. pyogenes. The most commonly isolated bacteria were H. influenzae in 31/99 (31%) and S. pneumoniae in 30/99 (30%) of samples. The majority of H. influenzae episodes were NTHi (27/31; 87%). 19F was the most frequently isolated pneumococcal serotype (10/30; 33%). Of the 30 S. pneumoniae positive samples, 8/30 (27%) were resistant to tetracycline, 5/30 (17%) to erythromycin and 8/30 (27%) had intermediate resistance to penicillin. All H. influenzae isolates tested were negative to beta-lactamase., Conclusions: NTHi and S. pneumoniae are the leading causes of AOM in Colombian children. A pneumococcal conjugate vaccine that prevents both pathogens could be useful in maximizing protection against AOM.

Determining which demographic and medical variables predict the development of hypertension could help clinicians stratify risk in both prehypertensive and nonhypertensive persons. Subject-level data from 2 community-based biracial cohorts were combined to ascertain the relationship between baseline characteristics and incident hypertension. Hypertension, defined as diastolic blood pressure ≥90 mm Hg, systolic blood pressure ≥140 mm Hg, or reported use of medication known to treat hypertension, was assessed prospectively at 3, 6, and 9 years. Internal validation was performed by the split-sample method with a 2:1 ratio for training and testing samples, respectively. A scoring algorithm was developed by converting the multivariable regression coefficients to integer values. Age, level of systolic or diastolic blood pressure, smoking, family history of hypertension, diabetes mellitus, high body mass index, female sex, and lack of exercise were associated with the development of hypertension in the training sample. Regression models showed moderate to high capabilities of discrimination between hypertension vs nonhypertension (area under the receiver operating characteristic curve 0.75-0.78) in the testing sample at 3, 6, and 9 years of follow-up. This risk calculator may aide health care providers in guiding discussions with patients about the risk for progression to hypertension., (© 2010 Wiley Periodicals, Inc.)

Rotavirus vaccination was introduced in Brazil in March 2006. We describe trends in hospitalizations from all-cause gastroenteritis in children younger than 5 years during pre- and postvaccination periods using hospital discharge data from Brazil Hospital Information System (SIH-SUS). A reduction in gastroenteritis hospitalizations of 26% and 48% in 2006 and in 2007, respectively, was observed among children younger than 1 year compared with prevaccination period (1998-2005). The largest reduction rates among children younger than 1 year were noted in the South and Southeast regions, approximately 56% in 2007, where vaccine coverage was the highest.

Background and Objectives: Endemic renal insufficiency (RI) of unknown etiology is a major public health issue with high mortality in the Pacific coastal regions of Central America. We studied RI in León and Chinandega, Nicaragua, evaluating associations with known risk factors and hypothesized exposures., Methods: A cross-sectional survey was conducted with assessment of medical, social, and occupational history and exposures in conjunction with measurement of serum creatinine. Cases were defined by an estimated glomerular filtration rate (eGFR) 140 or diastolic blood pressure (DBP) > 90 mmHg, or in reporting diabetes. Agricultural labor was associated with RI (OR = 2.48, 95%CI: 1.59, 3.89, p < 0.0001). There was no association with agricultural non-field work (OR = 0.91, 95%CI: 0.60, 1.38, p = 0.65). Consumption of unregulated alcohol ("lija") was associated with RI (OR = 2.10, 95%CI: 1.31, 3.39, p = 0.0023), as was drinking 5 L or more of water per day (OR = 3.59 vs. 1 L 95%CI: 1.52, 4.46, p = 0.0035)., Conclusions: Agricultural field labor and lija consumption were associated with RI in this region. Water intake may also be important. Identifying specific risk factors for RI within these exposures, such as individual pesticides or lija ingredients, may facilitate prevention in a setting where dialysis and transplantation are limited.

Tropical Storm Jeanne struck Haiti in September 2004, causing widespread flooding which contaminated water sources, displaced thousands of families and killed approximately 2,800 people. Local leaders distributed PūR, a flocculent-disinfectant product for household water treatment, to affected populations. We evaluated knowledge, attitudes, practices, and drinking water quality among a sample of PūR recipients. We interviewed representatives of 100 households in three rural communities who received PūR and PūR-related education. Water sources were tested for fecal contamination and turbidity; stored household water was tested for residual chlorine. All households relied on untreated water sources (springs [66%], wells [15%], community taps [13%], and rivers [6%]). After distribution, PūR was the most common in-home treatment method (58%) followed by chlorination (30%), plant-based flocculation (6%), boiling (5%), and filtration (1%). Seventy-eight percent of respondents correctly answered five questions about how to use PūR; 81% reported PūR easy to use; and 97% reported that PūR-treated water appears, tastes, and smells better than untreated water. Although water sources tested appeared clear, fecal coliform bacteria were detected in all sources (range 1 - >200 cfu/100 ml). Chlorine was present in 10 (45%) of 22 stored drinking water samples in households using PūR. PūR was well-accepted and properly used in remote communities where local leaders helped with distribution and education. This highly effective water purification method can help protect disaster-affected communities from waterborne disease.

Background: The association of cigarette smoking with albuminuria has been reported but not examined in a representative U.S. population. No study has evaluated the association between serum cotinine (a biological marker for tobacco exposure) and kidney damage., Methods: A cross-sectional analysis was conducted among 15,719 adult participants of the third National Health and Nutrition Examination Survey to assess the association between smoking exposure and kidney damage. Smoking was assessed by self-reported lifetime cigarette use and serum cotinine. Kidney damage was assessed by urine albumin-to-creatinine ratio (ACR), with albuminuria defined as ACR of > or =17 microg/mg in males and > or =25 microg/mg in females., Results: The analysis included 13,121 with normal albumin (mean ACR 6.3 microg/mg) and 2,414 with albuminuria (mean ACR 143 microg/mg); hypertension was prevalent in 27% and 59%, respectively. Former smoking was similar between groups (21%), while current smoking was more common in persons with albuminuria (26%) compared to normal ACR (21%). Adjusted for other risk factors, among hypertensives, current smokers were 1.85 (95% CI: 1.29, 2.64) times more likely to have albuminuria than never smokers. Current smokers with a > or =40 pack-year history were at highest risk for albuminuria. Among non-smoking hypertensives, those exposed to passive smoke (highest versus lowest quartile of serum cotinine) were 1.41 (95% CI: 1.04, 1.90) times more likely to have albuminuria. Former smoking with cessation of > or =1 year among hypertensives was not associated with albuminuria. Among non-hypertensives, smoking and albuminuria were not consistently associated., Conclusion: Current and passive smoking, but not former smoking, were associated with the presence of albuminuria in the general U.S. population with hypertension, indicating a benefit to the kidney from smoking cessation.

Purpose: Research on the risk of cardiovascular disease among individuals with prehypertension (blood pressure 120/80 to 139/89 mm Hg) is incomplete. Additional information among individuals with a high risk of cardiovascular disease complications may help to focus current and future efforts., Subjects and Methods: We performed a prospective cohort analysis among 8960 middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study. The exposure variables were blood pressure levels: high normal blood pressure, systolic blood pressure 130-139 mm Hg or diastolic blood pressure 85-89 mm Hg; and normal blood pressure, systolic blood pressure 120-129 mm Hg or diastolic blood pressure 80-84 mm Hg. The outcome was incident cardiovascular disease defined as fatal/nonfatal coronary heart disease, cardiac procedure, silent myocardial infarction, or ischemic stroke. Subgroup analysis was performed among blacks, diabetics, individuals aged 55-64 years, individuals with renal insufficiency, and among individuals with varying levels of low-density lipoprotein (LDL) cholesterol and body mass index (BMI)., Results: Compared with optimal blood pressure (systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg), the relative risk (RR) of cardiovascular disease for high normal blood pressure was 2.33 (95% confidence interval [CI], 1.85-2.92), and RR for normal blood pressure was 1.81 (1.47-2.22); among blacks: RR for high normal blood pressure was 3.29 (95% CI, 1.68-6.45); among diabetics: RR for high normal blood pressure 4.10 (95% CI, 2.26-7.46); age 55-64 years: RR for high normal blood pressure 2.41 (95% CI, 1.75-3.30) among individuals with renal insufficiency: RR for high normal blood pressure was 1.90 (95% CI, 1.34-2.70); among individuals with BMI >30 kg/m2: RR for high normal blood pressure was 3.56 (95% CI, 1.99-6.35); and among individuals with LDL >160 mg/dL, RR for high normal blood pressure was 1.85 (95% CI, 1.26-2.72)., Conclusions: Individuals with prehypertensive levels of blood pressure have an increased risk of developing cardiovascular disease relative to those with optimal levels. The association is pronounced among blacks, among individuals with diabetes mellitus, and among those with high BMI.

Background: Epidemiological studies suggest that dyslipidemia is an independent risk factor for the development of renal insufficiency in otherwise healthy individuals. Yet, data on the effect of cholesterol reduction are lacking in this population. We performed a secondary analysis of a large existing cohort to determine whether treatment with cholestyramine improved renal function compared with placebo., Methods: A total of 3,603 middle-aged men from the Lipid Research Clinics Coronary Primary Prevention Trial comprised the study group: 1,806 men were randomly assigned to treatment with cholestyramine, and 1,797 men, placebo. The primary outcome is difference in glomerular filtration rates between the 2 groups., Results: A total of 1,806 men were randomly assigned to treatment with cholestyramine, and 1,797 men, placebo. For the entire group, the estimated mean difference in glomerular filtration rates between the cholestyramine and placebo groups was 0.39 mL/min/1.73 m2 (0.007 mL/s/1.73 m2; P = 0.28) during a follow-up period of more than 8 years., Conclusion: Cholesterol reduction with cholestyramine treatment did not meaningfully affect renal function compared with placebo in the present analysis. Prospective intervention trials are needed to determine whether decreasing serum cholesterol levels benefits kidney function in otherwise healthy individuals.

Introduction: Chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (CVD) are often both present in selected populations. The independent association of early renal disease and atherosclerosis has not been studied in the general population. We hypothesized that the presence of low ankle brachial index (ABI), a surrogate measure of atherosclerotic cardiovascular disease, is associated with a low estimated glomerular filtration rate (GFR)., Methods: The study population consisted of 14,917 middle-aged black and white men and women from the Atherosclerosis Risk in Communities (ARIC) Study. An ABI<0.90 was defined as the exposure, and an estimated GFR<90 mL/min/1.73 m2 was defined as the outcome. Logistic regression analysis was performed cross-sectionally using an ABI of 1.00-1.19 as the reference, and was adjusted for the usual cardiovascular risk factors., Results: The presence of an ABI<0.90 was associated with an increased odds of having an estimated GFR<90 (OR: 1.80; 95% C.I.: 1.40-2.32) compared to the reference group. After adjustment, an ABI<0.90 remained significant, and increased the odds of having an estimated GFR<90 (OR: 1.54; 95% C.I.: 1.17-2.04) compared to the reference group. The odds ratio for GFR<90 was higher among African Americans than Whites, 1.88 versus 1.36 respectively., Discussion: This study gives support to the independent association of early CKD and atherosclerotic CVD. The relationship appears to be stronger among African Americans than among Whites. It will be necessary to investigate this observation more fully with prospective studies given the rising incidence of CKD.

The authors report the first case of immunotactoid glomerulopathy (ITG) in a human immunodeficiency virus (HIV)-positive, hepatitis B- and C-negative African-American man who presented with hematuria and proteinuria. His initial presentation was compatible with HIV associated nephropathy, but on renal biopsy he was found to have ITG. He has been treated with highly active antiretroviral therapy and an angiotensin-converting enzyme inhibitor, but his proteinuria has not responded after 4 months of treatment. This case emphasizes the diverse glomerular lesions seen in HIV-positive patients and supports the use of renal biopsy to establish a diagnosis.

Clinical trials have shown the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in delaying the progression of diabetic renal disease. There is less evidence from primary clinical trials of nondiabetic renal disease. We performed an updated meta-analysis to determine the efficacy of ACE inhibitors in slowing the progression of renal disease over a broad range of functional renal impairment. We included published and unpublished randomized, placebo-controlled, parallel trials with at least 1 year of follow-up available from January 1970 to June 1999. In nine trials of subjects with diabetic nephropathy and microalbuminuria, the relative risk for developing macroalbuminuria was 0.35 (95% confidence interval [CI], 0.24 to 0.53) for individuals treated with an ACE inhibitor compared with placebo. In seven trials of subjects with overt proteinuria and renal insufficiency from a variety of causes (30% diabetes, 70% nondiabetes), the relative risk for doubling of serum creatinine concentration or developing end-stage renal disease was 0.60 (95% CI, 0.49 to 0.73) for individuals treated with an ACE inhibitor compared with placebo. Treatment of individuals with chronic renal insufficiency with ACE inhibitors delays the progression of disease compared with placebo across a spectrum of disease causes and renal dysfunction.

This study evaluates the MR appearance of the kidney in diffuse renal parenchymal diseases, using precontrast, and immediate and delayed postgadolinium chelate (Gd), spoiled gradient echo (SGE), and pre- and post-Gd, T1-weighted, fat-suppressed spin-echo MR images to determine if characteristic findings exist for various types of renal disease. One hundred twenty-one patients with renal disease underwent MRI. Underlying diagnoses included: (a) glomerular disease (GD), (b) tubulointerstitial disease (TID), (c) microvascular disease (MVD), (d) ischemic nephropathy (INP), (e) obstructive nephropathy (ON), (f) infectious renal disease (IRD), (g) sickle cell disease (SCD), (h) renal cortical necrosis (CN), and (i) renal insufficiency of unknown etiology (UE). MR examinations of 22 patients with normal kidneys (NK) were evaluated as a control group. The presence of corticomedullary differentiation (CMD) demonstrated strong inverse correlation with serum creatinine concentration (SCr) (r = -.568, P < .001). Mean thickness of the renal cortex was 8.4 and 7.8 mm in patients with NK and Gd, respectively. The mean cortical thickness in patients with MVD, TID/Chemo, INP, and ON was 5.2, 5.6, 5.5, and 4.3 mm, respectively, significantly thinner than the renal cortex in the NK and GD groups (P < .01). Irregularity of the renal cortex was more frequent in MVD (60.9%), IRD (62.5%), ON (55.6%), and TID/other (53.8%) than in GD (3.8%) and NK (0%) (P < .01). Diffuse high SI of the entire medulla on delayed postcontrast images was observed in 25 (20.7%) of the patients with renal disease and none of the NK group. Although no pathognomonic features were found, certain findings were observed that may correlate with the etiology of the kidney disease and, therefore, assist in the differential diagnosis of renal parenchymal disease.

Purpose: To evaluate renal corticomedullary differentiation (CMD) in patients with differing serum creatinine (sCr) levels., Materials and Methods: Ten patients with normal sCr levels (0.9-1.3 mg/dL [80-115 mumol/L]), 14 with mildly elevated levels (1.5-2.9 mg/dL [133-256 mumol/L]), and 15 with elevated levels (> 3.0 mg/dL [265 mumol/L]) were examined with unenhanced T1-weighted fat-suppressed spin-echo (T1FS) and immediate gadolinium-enhanced gradient-echo (Gd-GRE) imaging., Results: Patients with normal sCr levels had CMD on T1FS and Gd-GRE images. Among patients with mildly elevated levels, seven did and seven did not have CMD on T1FS images; all had CMD on Gd-GRE images. Patients with elevated levels had no CMD on T1FS images; 13 had CMD on Gd-GRE images. Two patients with levels above 10.0 mg/dL (884 mumol/L) had no CMD on Gd-GRE images., Conclusion: Independent of the cause of elevated sCr level, levels above 3.0 mg/dL result in loss of CMD on T1FS images, while levels above 10.0 mg/dL result in loss of CMD on Gd-GRE images.

Transient diabetes insipidus of pregnancy (TDIP) is associated with elevated activity of vasopressinase, a plasma enzyme that opens the vasopressin (AVP) ring to produce a linear peptide that we have named vasopressinase-altered vasopressin (VAV). VAV may play a role in the pathogenesis of the arterial hypertension associated with TDIP. We sought to determine if VAV elevates arterial pressure, the potency of VAV relative to that of AVP, and whether the peptide binds to the vascular AVP receptor. AVP was incubated with vasopressinase and VAV was separated from residual AVP by high-pressure liquid chromatography. Intravenous bolus administration of VAV or AVP to ganglionic blocked rats produced dose-dependent increases in arterial pressure, with VAV demonstrating approximately 6000-fold lower potency than AVP. Vasopressin receptor blockade abolished the response to both AVP and VAV. These results suggests that high levels of VAV may contribute to the hypertension seen in TDIP.

This study was designed to investigate the effects of bilateral renal denervation on sodium and water balance, the renin-angiotensin system, and systemic blood pressure in unrestrained conscious rats maintained on a normal- or low-sodium diet. Renal denervation was proven by chemical and functional tests. Both bilaterally denervated rats (n = 18) and sham-denervated rats (n = 15) maintained positive sodium balance while on a normal sodium intake. Both groups were in negative sodium balance for 1 day after dietary sodium restriction was instituted but were in positive sodium balance for the following 9 days. Systolic blood pressure was higher in sham-denervated (115 +/- 3 mmHg) than in denervated rats (102 +/- 3 mmHg) while on a normal diet (P less than 0.05) and remained so during sodium restriction. Plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were significantly diminished in the denervated rats during normal sodium intake (P less than 0.05). After dietary sodium restriction, PRC increased in both groups but remained significantly lower in the denervated rats (P less than 0.05). Following dietary sodium restriction, PAC also increased significantly to levels that were similar in both groups of rats. These results demonstrate that awake unrestrained growing rats can maintain positive sodium balance on a low sodium intake even in the absence of the renal nerves. However, efferent renal nerve activity influenced plasma renin activity in these animals.

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and chronic bilateral denervated kidneys after cholinergic stimulation of the anterior part of the lateral hypothalamus. Denervation was produced in anesthetized and conscious nondiuretic rats by application of phenol to the renal artery. Studies were also performed in sham denervated rats. Whole kidney function in anesthetized animals showed a significant increase of fractional sodium excretion (0.7 +/- 0.1 to 1.7 +/- 0.4%, P less than 0.01) both in the denervated and in the innervated kidney (0.09 +/- 0.02 to 1.1 +/- 0.2%, P less than 0.005) after carbachol injection into the LHA, whereas the percentage of filtered potassium excreted increased only in the innervated kidney (11.4 +/- 1.3 to 16.3 +/- 1.1%, P less than 0.01). Similarly, in conscious rats, fractional sodium excretion increased after cholinergic stimulation in animals having denervated kidneys (2.1 +/- 0.1 vs 3.6 +/- 0.2%, P less than 0.005). Fractional potassium excretion also increased both in rats with sham-denervated and denervated kidney. There was an acute elevation in mean arterial blood pressure and glomerular filtration rate (GFR) during the first 20-min after carbachol injection. Sodium excretion was statistically significant during the three 20-min collections of the experimental period. This suggests that the natriuresis is not associated with increased arterial pressure, GFR or renal plasma flow. Our results indicate that natriuresis occurs even in the absence of the renal nerves.

Sodium (Na), calcium (Ca), inorganic phosphate (Pi) and water excretion were measured in nondiuretic (ND) and extracellular fluid (ECF) volume expanded (VE) conscious restrained rats four weeks after denervation or sham-denervation of the left kidney. On the day of the study the animals were lightly anaesthetized with ether and the femoral vessels on one side were catheterized. Urine was collected from both kidneys. The animals were allowed to recover for 3 hours and studied in a restraining chamber. In ND animals isotonic saline containing inulin and para-amino-hippuric acid (PAH) were given at a rate of 0.067 +/- 0.002 (SE) ml/min/kg body weight (BW). In VE animals the infusion rate was 0.24 +/- 0.04 ml/min/kg BW. Kidney catecholamine content was measured after the experiments. Clearances of PAH and of inulin (GFR) were the same in both kidneys. Urine volume (V), sodium excretion (UNa V/GFR), inorganic phosphate excretion (UPi V/GFR) and calcium excretion (UCa V/GFR) were significantly higher in the denervated kidneys. Values in sham denervated kidneys were not greater than those of the right kidney. Denervation was proven by demonstrating absent or very low catecholamine content in the kidneys. The results demonstrate that: chronic renal denervation in rats leads to diuresis and natriuresis even in the conscious state, thus confirming previous results from our laboratory; such changes occur independently of the state of the ECF volume and of renal haemodynamic changes; the increased excretion of Ca++ and Pi after denervation demonstrates that renal nerves affect the reabsorption of these ions either independently or by way of their effect on sodium reabsorption. These data allow us to suggest that a renal tubular dysfunction, which was proved in anaesthetized denervated animals, can also be observed in the conscious state.

The mechanism of the vasodilatory action of carvedilol (BM 14190), a new antihypertensive agent, was investigated in normal volunteers. Intra-arterial blood pressure and ECG were monitored continuously. Carvedilol (1 mg/min for 15 minutes) produced a rapid reduction in blood pressure and a transient increase in heart rate. At the end of infusion, systolic and diastolic blood pressure were reduced by 23% (-32.3 mm Hg) and 18% (-13.6 mm Hg), respectively, whereas heart rate was not different from baseline. At the doses used, the hypotensive effect of carvedilol was greater than that of labetalol (36 and 72 mg in 15 minutes). Carvedilol and labetalol antagonized isoproterenol-induced hypotension and tachycardia, at serum levels greater than or equal to 8 and 20 mg/ml, respectively. Both drugs antagonized phenylephrine pressor effects. A similar degree of inhibition (25% of control) of pressor effects was observed for carvedilol and labetalol when their respective serum concentrations were 23 ng/ml and 80 ng/ml. Neither carvedilol nor labetalol had any effect on AII pressor responses. Carvedilol serum levels as high as 150 ng/ml failed to inhibit AII-induced pressor responses. Our results suggest that at the doses used in this study, carvedilol has both alpha 1-and nonselective beta-receptor blocking properties. Moreover, carvedilol is approximately three to five times more potent than labetalol in blocking alpha 1-and beta-receptors and in reducing blood pressure.

The role of the renal nerves in the natriuresis seen after cholinergic stimulation of the hypothalamus was studied in anesthetized rats treated with injection into the lateral hypothalamus (LH) of 1 microgram of carbamylcholine chloride (carbachol) in 1 microliter of 0.15 M NaCl or NaCl alone. Injection of carbachol exhibited diuresis and natriuresis both in acutely denervated kidneys (P less than 0.01) and in contralateral innervated kidneys (P less than 0.01) without changes in glomerular filtration rate (GFR) or renal plasma flow (RPF) (n = 10). Salt and water excretion was unchanged in 10 rats after injection of NaCl. Micropuncture studies in denervated kidneys showed that, after carbachol injection, tubular fluid-to-plasma inulin concentration ratio [(F/P)In] in the late proximal tubule fell from 1.86 +/- 0.08 to 1.64 +/- 0.07 (P less than 0.01) without changes in single-nephron GFR. In nine other carbachol-treated rats in which renal perfusion pressure was maintained low and constant, diuresis and natriuresis, although attenuated, were again observed both in denervated (P less than 0.01) and in contralateral innervated kidneys (P less than 0.05). In another group of 11 animals, efferent renal nerve activity (ERNA) was recorded before and after LH injection of carbachol and isotonic saline. ERNA was significantly depressed for 30 min, only after carbachol injection. Our results suggest that the renal nerves, although involved, are not essential for the natriuretic response after cholinergic stimulation of LH. By exclusion, other factors, presumably hormones, must contribute to the response.

We investigated possible mechanisms for the natriuresis seen after injection of the cholinergic drug carbamylcholine chloride (carbachol) into the lateral hypothalamus of conscious rats. In unrestrained rats injection of 1 microgram of carbachol in 1 microliter of 0.15 M NaCl solution through a permanently implanted cannula produced a significant natriuresis and kaliuresis. Injection of vehicle produced no changes. The same animals were then subjected to bilateral renal denervation (n = 13) or sham denervation (n = 13) and injected with the same solutions 1 wk later. Carbachol injection produced a natriuresis (P less than 0.0001) and a kaliuresis (P less than 0.01) in all animals studied. Both responses were of a magnitude similar to the responses seen before denervation. We studied other rats while awake but restrained, which permitted the performance of clearance studies and blood pressure measurements. Injection of carbachol produced diuresis, natriuresis, and kaliuresis in all rats, with no change in p-aminohippurate clearance and only transient change in inulin clearance. An increase in blood pressure occurred in some but not all rats. The response in rats with bilaterally denervated kidneys (n = 7) was similar to that of rats with innervated kidneys (n = 5). The natriuresis seen after cholinergic stimulation of the hypothalamus in conscious rats is not primarily mediated by inhibition of renal nerve activity and can be dissociated from changes in blood pressure, glomerular filtration rate, and renal plasma flow.

In a single blind parallel design, saline (n = 9), labetalol i.v. (40 mg n = 4, 80 mg n = 3), and carvedilol i.v. (15 mg n = 8) were given to volunteers with blood pressure (BP) recorded intraarterially. The effect of these treatments on the response to challenge doses of angiotensin II (to give a rise in mean BP of 20-25 mm Hg), isoproterenol (to give an increase in heart rate of 30-35 beats/min), and phenylephrine (to give a rise in mean BP of 20-25 mm Hg) were studied. The dose of i.v. carvedilol employed gave a greater fall in BP than the dose of labetalol used. Carvedilol appeared to be about four times more potent than labetalol in inhibiting the tachycardia to isoprenaline. Likewise, from inhibition of the pressor response to phenylephrine, it is concluded that carvedilol is four times more effective at the alpha receptor than labetalol. Neither drug was found to antagonize the pressor effects of angiotensin. Calculation of the half-life of carvedilol gave values of 2.2 to 9 h. The volume of distribution was found to be 1.54 l/kg and the total body clearance was 0.521 l/h/kg.

Sodium reabsorption along the nephron was studied before and after acute unilateral denervation of the left kidney in anesthetized rats with extracellular volume expansion. Studies were also performed before and after sham denervation. Denervation increased urine volume (V) from the left kidney from 35.2 to 59.2 mul min-1 (P less than 0.001) and urinary sodium excretion (UNaV) from 6.9 to 11.8 mueq min-1 (P less than 0.001). The control right kidney showed a simultaneous 45% decrease in V and UNaV. Inulin clearance (GFR) and renal plasma flow (RPF) remained unchanged after denervation in both kidneys. Left kidney late proximal (F/P)m decreased from 1.50 to 1.24 (P less than 0.01); single-nephron GFR (SNGFR) remained unchanged. (F/P)m ratios were also decreased in early distal (3.87-2.65, P less than 0.005) and late distal (5.48-3.83, P less than 0.02) convolutions. Fractional and absolute Na reabsorption in the distal convolution did not decrease. GFR, RPF, V, UNa, late proximal (F/P)m, and SNGFR were unchanged in sham-denervated rats. The increases in V and UNa V produced by acute renal denervation in the volume-expanded anesthetized animal are thus caused by further depression of proximal tubular salt and water reabsorption.

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P less than 0.001) and increased urinary sodium excretion from 332 neq min minus -1 to 1,887 neq min minus -1 (P less than 0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [(F/P)In] decreased from 2.23 to 1.50 (P less than 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 n. min minus -1 (P less than 0.001). (F/P)In ratios were also decreased in early distal (from 6.21 to 3.18, P less 0.001) and late distal convolutions (from 16.41 to 8.33, P less than 0.001) during the experimental period. (F/P)Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 (P less than 0.01) in late distal convolutions after denervation. Absolute Na reabsorption after denervation increased in the loop of Henle, distal convolution, and collecting ducts. Any changes in intrarenal hydrostatic pressures after denervation were always small. There were no changes in GFR, RPF, urine volume, urinary sodium excretion, or late proximal (F/P)In after sham denervation. We conclude that the diuresis and natriuresis seen after acute renal denervation were caused by a marked depression of sodium and water reabsorption in the proximal tubule with partial compensation in more distal nephron segments. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes. The results demonstrate an effect of the renal nerves on proximal tubular function.

Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresis and natriuresis in 19 animals. A simultaneous decrease of glomerular filtration rate, p-aminohippurate clearance, urinary volume (P < 0.002), and percentage of filtered sodium excreted (4.0 +/- 0.6 (SE) vs. 1.9 +/- 0.4%, P < 0.003) occurred in the right innervated kidney in 10 rats. Prior denervation of the right kidney in the other nine rats prevented the renal hemodynamic changes and the fall of urinary volume and of sodium excretion (3.9 +/- 0.6 vs. 4.3 +/- 0.5%) by the right kidney after left renal denervation. Nerve traffic to the right kidney was measured in six other animals after left renal denervation and was found to increase to a mean value 33.8 +/- 6.3% above control levels (P < 0.007) 0-30 min after denervation, with a further significant increase to 66.2 +/- 16.1% above control levels (P < 0.025) 30-60 min after denervation. These results indicate that the functional changes in the right kidney after contralateral renal denervation in volume-expanded rats are caused by a reflex increase in nerve traffic to the right kidney, possibly as a consequence of an interruption of afferent nerve activity originating in the left kidney.

Renal vascular reactivity to intrarenal arterial boluses of norepinephrine (NE), phenylephrine (PHE; alpha 1-agonist), and guanabenz (GBZ; alpha 2-agonist) was assessed in conscious, freely moving, chronically instrumented, normotensive Wistar rats. Dose-response curves (DRCs) were obtained in the absence and cumulative presence of propranolol (PROP; beta-antagonist), corynanthine (CORY; alpha 1-antagonist) and idazoxan (IDX; alpha 2-antagonist) to estimate effective dosages (ED) required for 15 and 75% peak reductions in renal blood flow. The PHE DRC had a short shallow ED15 region, but was primarily linear with a steep slope. The GBZ DRC had a shallow slope. The NE DRC had a prolonged shallow phase in the ED15 region and a steep slope in the ED75 region. PROP had no effect on the DRCs. CORY caused a parallel rightward shift of the PHE DRC and had no effect on the GBZ DRC. After CORY, the shallow ED15 portion of the NE DRC was even more pronounced with a slope now identical to that of the GBZ DRC, whereas the ED75 region of the NE DRC was shifted rightward like the PHE DRC. IDX preferentially antagonized the ED15 regions of the GBZ and NE DRCs. In a second group of rats, the alpha 2-adrenoceptor antagonist, rauwolscine, was administered following base-line DRCs to demonstrate rightward shifts of the NE and GBZ DRCs when PHE DRCs remained unaffected. Therefore, when boluses of NE are injected into the rat kidney, the vasoconstrictive responses are a result of the activation of both alpha 1- and alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)