9 results on '"Raij, Leopoldo"'
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2. Angiotensin II, nitric oxide, and end-organ damage in hypertension.
- Author
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Bataineh, Ahnaf and Raij, Leopoldo
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ANGIOTENSIN-receptor blockers , *NITRIC oxide , *HYPERTENSION - Abstract
Examines the role of angiotensin II and nitric oxide in the prevention of end-organ damage in hypertension. Effects of angiostein II on vascular tone and growth; Interaction between nitric oxide and angiotensin II; Link between nitric oxide synthase activity and renal, vascular and cardiac injury.
- Published
- 1998
3. Angiotensin II, nitric oxide, and end-organ damage in hypertension.
- Author
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Bataineh, Ahnaf and Raij, Leopoldo
- Subjects
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HYPERTENSION , *ANGIOTENSIN II , *EXTRACELLULAR matrix , *KIDNEY failure , *ENDOTHELIUM - Abstract
Angiotensin II, nitric oxide, and end-organ damage in hypertension. The adaptive changes that accompany hypertension and involve the kidney, heart, and vessels, namely, muscle hypertrophy/hyperplasia, endothelial dysfunction and extracellular matrix increase can, in fact, be maladaptive and eventually lead to end- organ disease, such as renal failure, heart failure, and coronary disease. However, these changes vary markedly between individuals with similar levels of hypertension. Nitric oxide (NO), an endogenous vasodilator and inhibitor of vascular smooth muscle and mesangial cell growth, is synthesized in the endothelium by a constitutive NO synthase (NOS). NO antagonizes the effects of angiotensin II on vascular tone and growth and also down- regulates the synthesis of angiotensin converting enzyme (ACE) and angiotensin II type 1 (AT-1) receptors. In hypertension, the physiologic response to the increased shear stress and cyclic strain is to upregulate NOS activity in endothelial cells. Upregulation of vascular NOS activity is a homeostatic adaptation to the increased hemodynamic workload that may help in preventing end-organ damage. Indeed, hypertension-prone salt-sensitive rats manifest a decrease (instead of an increase) in vascular NOS activity when hypertensive; these rats develop severe vascular hypertrophy, left ventricular hypertrophy, and renal injury. Studies in hypertensive humans suggest that, independent of the effects of salt on blood pressure, salt sensitivity may be a marker for susceptibility to the development of endothelial dysfunction as well as cardiovascular and renal injury. We hypothesize that in hypertension, recognition of markers of cardiovascular susceptibility to injury and the understanding of the pathophysiological mechanisms involved may open new opportunities for therapeutic intervention. In this context, only those antihypertensive agents that lower blood pressure and concomitantly restore the homeostatic balance of vasoactive agents such as angiotensin II and NO within the vessel wall would be effective in preventing or arresting end-organ disease. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
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4. Angiotensin II induces superoxide anion production by mesangial cells.
- Author
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Jaimes, Edgar A., Galceran, Josep Maria, and Raij, Leopoldo
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SUPEROXIDES , *HEMODYNAMICS , *MITOGENS , *PROTEIN kinases - Abstract
Angiotensin II induces superoxide anion production by mesangial cells. Background. The recognized role of angiotensin II (Ang II) in the pathogenesis of the progression of renal disease cannot be solely attributed to Ang II's hemodynamic effects. Indeed, growth stimulating signals driven by Ang II promote mesangial cell (MC) hypertrophy and extracellular matrix production, prominent features of progressive glomerular injury. Superoxide anion (O2 - ) avidly interacts with nitric oxide, an endogenous vasodilator that inhibits growth factor stimulated MC growth and matrix production. In addition, O2 - acting as an intracellular signal is linked to growth related responses such as activation of mitogen activated protein (MAP) kinases. The studies reported herein were designed to investigate: (a ) whether Ang II induces MC O2 - production and (b ) if increased O2 - production elicits growth responses in MC. Methods. MC were exposed to Ang II for 24 or 48 hours. In some experiments, in addition to Ang II, MC were exposed to: diphenylenieodonium (DPI), an inhibitor of the flavin containing NADH/NADPH oxidase; losartan (LOS), an Ang II type 1 (AT1) receptor blocker; PD 98059, a MAP kinases inhibitor; the protein kinase C inhibitors Calphostin C or H-7; and the tyrosine kinase inhibitors, herbymycin A or genistein. Results. Ang II (10-5 M to 10-8 M) dose dependently increased MC O2 - production up to 125% above control (ED 50 5 × 10-7 M). LOS as well as DPI, and the PKC inhibitors blocked Ang II stimulated MC O2 - production. Ang II dose dependently increased MC 3 H-leucine incorporation, and MC protein content, two markers of MC hypertrophy, as well as 3 H-thymidine incorporation, a marker of MC hyperplasia. PD98059, a specific inhibitor of MAP kinases prevented Ang II induced MC... [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
5. Major and Minor Electrocardiographic Abnormalities and Their Association With Underlying Cardiovascular Disease and Risk Factors in Hispanics/Latinos (from the Hispanic Community Health Study/Study of Latinos).
- Author
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Denes, Pablo, Garside, Daniel B., Lloyd-Jones, Donald, Gouskova, Natalia, Soliman, Elsayed Z., Ostfeld, Robert, Zhu-Ming Zhang, Camacho, Alvaro, Prineas, Ronald, Raij, Leopoldo, and Daviglus, Martha L.
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ELECTROCARDIOGRAPHY , *CARDIOVASCULAR diseases risk factors , *HEALTH of Hispanic Americans , *PUERTO Ricans , *LONGITUDINAL method , *COHORT analysis , *COMPARATIVE studies - Abstract
The association of electrocardiographic (ECG) abnormalities with cardiovascular disease and risk factors has been extensively studied in whites and African-Americans. Comparable data have not been reported in Hispanics/Latinos. The Hispanic Community Health Study/ Study of Latinos (HCHS/SOL) is a multicenter, community-based, prospective cohort study of men and women of diverse backgrounds aged 18 to 74 years who self-identified as Hispanic/Latinos. Participants (n = 16,415) enrolled from March 2008 to June 2011. We describe the prevalence of minor and major ECG abnormalities and examined their cross-sectional associations with cardiovascular disease and risk factors. The Minnesota code criteria were used to define minor and major ECG abnormalities. Previous cardiovascular disease and risk factors were based on data obtained at baseline examination. Significant differences in prevalent ECG findings were found between men and women. Major ECG abnormalities were present in 9.2% (95% confidence interval 8.3 to 10.1) of men and 6.6% (95% confidence interval 5.8 to 7.3) of women (p <0.0001). The odds of having major ECG abnormalities significantly increased with age, presence of ≥3 cardiovascular risk factors, and prevalent cardiovascular disease, in both men and women. Significant differences in major ECG abnormalities were found among the varying groups; Puerto Ricans and Dominicans had more major abnormalities compared with Mexican men and women. In conclusion, in a large cohort of Hispanic/Latino men and women, prevalence of major abnormalities was low, yet strong associations of major ECG abnormalities with cardiovascular disease and risk factors were observed in both men and women. [ABSTRACT FROM AUTHOR]
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- 2013
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6. Sodium challenge does not support an acute gastrointestinal-renal natriuretic signaling axis in humans.
- Author
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Preston, Richard A, Afshartous, David, Forte, Leonard R, Rodco, Rolando, Alonso, Alberto B, Garg, Dyal, and Raij, Leopoldo
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PHYSIOLOGICAL effects of sodium , *NATRIURETIC peptides , *SALT-free diet , *SEROLOGY , *PROPROTEIN convertases - Abstract
A gastrointestinal-renal natriuretic signaling axis has been proposed to regulate sodium excretion in response to acute sodium ingestion. Such an axis is thought to be regulated by a gastrointestinal sodium sensor coupled to the activation/release of a natriuretic signal and could have important clinical and scientific implications. Here we systematically tested for this putative axis and the potential involvement of the gastrointestinal-derived natriuretic prohormones prouroguanylin and proguanylin in 15 healthy volunteers. There was no difference in sodium excretion following equivalent oral or intravenous sodium loads during either high- or low-sodium diets. Furthermore, serum concentrations of prouroguanylin and proguanylin did not increase, did not differ following oral or intravenous sodium, and did not correlate with sodium excretion. Thus, our results do not support an acute gastrointestinal-renal natriuretic axis or a central role for prouroguanylin or proguanylin in humans. If such an axis does exist, it is not characterized by a significant difference in the pattern of sodium excretion following either an oral or intravenous sodium load. [ABSTRACT FROM AUTHOR]
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- 2012
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7. Design and Implementation of the Hispanic Community Health Study/Study of Latinos
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Sorlie, Paul D., Avilés-Santa, Larissa M., Wassertheil-Smoller, Sylvia, Kaplan, Robert C., Daviglus, Martha L., Giachello, Aida L., Schneiderman, Neil, Raij, Leopoldo, Talavera, Gregory, Allison, Matthew, LaVange, Lisa, Chambless, Lloyd E., and Heiss, Gerardo
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HEALTH of Hispanic Americans , *PUBLIC health education , *EPIDEMIOLOGY , *WECHSLER Adult Intelligence Scale , *ACCULTURATION , *ASPARTATE aminotransferase , *BLOOD testing , *C-reactive protein , *DNA , *ELECTROCARDIOGRAPHY , *HIGH density lipoproteins , *HEPATITIS C virus - Abstract
Purpose: The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a comprehensive multicenter community based cohort study of Hispanics/Latinos in the United States. Methods: The Study rationale, objectives, design, and implementation are described in this report. Results: The HCHS/SOL will recruit 16,000 men and women who self-identify as Hispanic or Latino, 18 to 74 years of age, from a random sample of households in defined communities in the Bronx, Chicago, Miami, and San Diego. The sites were selected so that the overall sample would consist of at least 2000 persons in each of the following origin designations: Mexican, Puerto Rican and Dominican, Cuban, and Central and South American. The study includes research in the prevalence of and risk factors for heart, lung, blood and sleep disorders, kidney and liver function, diabetes, cognitive function, dental conditions, and hearing disorders. Conclusions: The HCHS/SOL will (1) characterize the health status and disease burden in the largest minority population in the United States; (2) describe the positive and negative consequences of immigration and acculturation of Hispanics/Latinos to the mainstream United States life-styles, environment and health care opportunities; and (3) identify likely causal factors of many diseases in a population with diverse environmental exposures, genetic backgrounds, and early life experiences. [Copyright &y& Elsevier]
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- 2010
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8. Up-regulation of glomerular COX-2 by angiotensin II: Role of reactive oxygen species.
- Author
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Jaimes, Edgar A., Run-Xia Tian, Pearse, Damien, and Raij, Leopoldo
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PROSTAGLANDINS , *PROSTAGLANDINS E , *GLOMERULAR filtration rate , *ANGIOTENSIN II , *REACTIVE oxygen species , *KIDNEY glomerulus , *HYPERTROPHY - Abstract
Background. Prostaglandins such as prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) counteract the angiotensin II (Ang II)–induced vasoconstriction in the glomerular microcirculation. We have shown that Ang II promotes mesangial cell hypertrophy via reactive oxygen species (ROS), which originate from nicotinamide adenine dinucleotide phosphate and its reduced form (NADH/NADPH) oxidase. It has been reported that conditions associated with activation of the renin-angiotensin system result in increased glomerular cyclooxygenase-2 (COX-2) expression and activity. Methods. We designed studies to determine ( 1) whether Ang II induces COX-2 in the glomerulus in vivo in the glomerulus as well as in vitro in mesangial cells, ( 2) whether ROS originated from Ang II are involved, and ( 3) whether COX-2–derived prostaglandins modulate the growth promoting effects of Ang II in mesangial cells. Rats were infused with Ang II (0.7 mg/kg/day) for 5 days and glomerular COX-2 expression and activity assessed in isolated glomeruli. Results. Ang II increased glomerular PGE2 production (100%) accompanied by a concomitant increase in glomerular COX-2 expression at the mRNA (1.7-fold) and protein level (sixfold). In mesangial cells, Ang II significantly increased mesangial cell PGE2 (200%) and PGI2 (100%) production as well as COX-2 mRNA that was prevented by the angiotensin type 1 (AT1) receptor blocker irbesartan and the COX-2 inhibitor NS-398. The NADPH oxidase inhibitor diphenyleneiodonium (DPI), the ROS scavenger tiron as well as catalase, inhibited Ang II–induced PGE2 production suggesting that Ang II–induced ROS mediate COX-2 up-regulation. Strikingly, COX-2 inhibition as well as blockade of the type 1 PGE2 receptor (EP1) prevented Ang II–induced mesangial cell hypertrophy suggesting that COX-2–derived prostaglandins, and specifically PGE2, importantly contribute to the growth promoting effects of Ang II. Conclusion. These studies suggest that blockade of specific PGE2 receptors may be a novel strategy to modulate the pathologic effects of COX-2–derived prostaglandins without simultaneously affecting protective vasodilatory mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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9. The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients.
- Author
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Grossman, Eric B., Swan, Suzanne K., Muirhead, Gary J., Gaffney, Michael, Chung, Menger, Deriesthal, Herb, Chow, Diane, and Raij, Leopoldo
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HEMODIALYSIS patients , *HEMODYNAMICS , *PHARMACOKINETICS , *CITRATES , *SILDENAFIL , *IMPOTENCE , *CHRONIC kidney failure - Abstract
The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients. Background. Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. Methods. Fifteen men undergoing chronic outpatient maintenance hemodialysis received a single 50-mg oral dose of sildenafil on 2 occasions, once 2 hours before, and once 2 hours after hemodialysis, with randomized assignment to sequence. Blood and dialysate samples were collected, and hemodynamic measurements were made. Results. Hemodialysis did not significantly clear either sildenafil or its primary metabolite, UK-103,320. Administration after hemodialysis was associated with a 17% higher peak plasma concentration and earlier time to peak, which were not clinically meaningful, whereas the overall extent of absorption and the elimination half-life were not affected. The average extent of drug bound to plasma protein was approximately 96% in hemodialysis patients. Intradialytic hypotension was not observed more frequently when sildenafil was administered before hemodialysis. Systolic blood pressure tended to decrease less during hemodialysis when subjects were treated with sildenafil before dialysis. Conclusion. The present study demonstrates that sildenafil is not cleared by hemodialysis, and the pharmacokinetic profile resembles more closely that observed in normal volunteers than that observed in patients with severe renal insufficiency. In addition, we found that sildenafil does not promote intradialytic hypotension. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
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