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Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.

In hypertension, an increased media-to-lumen ratio of small resistance arteries might play an important role in the increase of vascular resistance, and may also be an adaptive response to the increased hemodynamic load. The presence of morphological alteration in the microvasculature may be associated to an impaired tissue perfusion and/or to the development of target organ damage. Structural alterations in the microcirculation might represent a predictor of the onset of cardio-cerebrovascular events and hypertension complications. A cross-talk between the small and large artery may exaggerate arterial damage, following a vicious circle. Therefore, in the present review, possible hemodynamic consequences of the presence of microvascular structural alterations will be considered, in terms of their time of onset, role in the development and/or maintenance of high blood pressure values, and interrelationships with structural/mechanical alterations of large conductance arteries., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Arterial hypertension (HTN) accounts for the largest amount of attributable cardiovascular (CV) mortality worldwide, and risk stratification in hypertensive patients is of crucial importance to manage treatment and prevent adverse events. Asymptomatic involvement of different organs in patients affected by HTN represents an independent determinant of CV risk and the identification of target organ damage (TOD) is recommended to further reclassify patients' risk. Non-invasive CV imaging is progressively being used and continues to provide new technological opportunities to TOD evaluation at early stage. The aim of this article is to provide the community of cardiology with an update on appropriate and justified use of non-invasive imaging tests in the growing population of hypertensive patients., (© The Authors, 2017. This article has been co-published in European Heart Journal - Cardiovascular Imaging and Journal of Hypertension The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

Background: Different components of the immune system, including innate and adaptive immunity (T-effector lymphocytes and T-regulatory lymphocytes-TREGs) may be involved in the development of hypertension. In addition, it was demonstrated in animal models that TREGs may prevent angiotensin II-induced hypertension and vascular injury/inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular structural alterations., Methods: For this purpose, in the present study, we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and the media to lumen ratio (M/L) was calculated. In addition, retinal arteriolar structure was evaluated noninvasively by scanning laser Doppler flowmetry. Capillary density in the nailfold, dorsum of the finger, and forearm were evaluated by videomicroscopy. A peripheral blood sample was obtained before surgery for assessment of T-lymphocyte subpopulations by flow cytometry., Results: Significant negative correlations were observed between indices of microvascular structure (M/L of subcutaneous small arteries and wall to lumen ratio of retinal arterioles) and circulating TREG lymphocytes. A direct correlation was observed between M/L of subcutaneous small arteries and circulating Th17 lymphocytes. In addition, total capillary density was correlated with a TREG effector memory subpopulation., Conclusion: Our data suggest that some lymphocyte subpopulations may be related to microvascular remodeling, confirming previous animal data, and opening therapeutic possibilities., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: It has been suggested that in animal models, red wine may have a protective effect on the vascular endothelium. However, it is not known whether this effect is also present in human small vessels and whether it is specific for certain wines. The objective of this study is to compare the vasodilator effects in subcutaneous small resistance arteries of wines with different flavonoid content as well as of ethanol vs. wines in normotensive (NT) subjects and in patients with essential hypertension (EH)., Methods: Twenty-six EH and 27 NT were included in the study. Subcutaneous small resistance arteries were dissected and mounted on a micromyograph. Then we evaluated vasodilator responses as concentration-response curves (20, 30, and 50 microl) to the following items: (i) a red wine produced in small oak barrels ("en barrique": EB) (Barolo Oberto 1994), (ii) a red wine produced in large wood barrels (LB) (Barolo Scarzello 1989), (iii) a red wine produced in steel tanks (Albarello Rosso del Salento 1997), and (iv) a white wine produced in steel tanks in the presence or absence of an inhibitor of the nitric oxide (NO) synthase (L-NMMA 100 micromol/l)., Results: A dose-dependent vasodilator effect of red wines (particularly EB and LB) was detected in both NT and HT. The observed response was not reduced after preincubation with L-NMMA., Conclusions: Our results suggest red wines are more potent vasodilator than ethanol alone, possibly depending on the content of polyphenols or tannic acid. HT show similar responses compared with NT, indicating that red wine is not harmful in this population.

Context: The leucine-75-proline variant of apolipoprotein A-I leads to a new hereditary systemic amyloidosis involving mostly the liver and kidney., Objective: The objective of the study was to examine the effects of this amyloidosis on testicular structure and function., Design: This was an observational study in which patients with testicular amyloidosis were characterized., Setting: The study was carried out at the Endocrinology Department of Brescia University., Patients or Other Participants: Over a 13-yr period, 25 patients were found to be affected by leucine-75-proline apolipoprotein A-I testicular amyloidosis. Thirteen had the testicle as the first or only organ involved (group 1); in 12 testicular damage followed that of other organs (group 2)., Interventions: There were no interventions., Main Outcome Measure: Hormone and lipidic profiles, semen analysis, echographic volume of testicles, testicular histology, and genetic analysis were carried out., Results: Group 1 patients were younger than those of group 2. In group 1, eight had hypergonadotropic hypogonadism and five were normogonadic with high gonadotropins; in group 2 all subjects were hypogonadic. All men had low high-density lipoprotein values. Group 1 patients were macroorchid, whereas the testicular volume was at the highest limit in group 2 (group 1 vs. group 2, P < 0.05). All men in the first group and six in the second group were azoospermic; the remaining had oligoposia. Biopsies showed the germinal epithelium replaced by amyloid. Leydig cells were essentially preserved in normogonadic but not hypogonadic patients., Conclusions: This amyloidosis may determine infertility, macroorchidism, and hypogonadism. Endocrine impairment follows spermatogenic impairment.

Background: Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased tunica media to internal lumen ratio of subcutaneous small-resistance arteries (M:L) may predict the development of cardiovascular events in a high-risk population. However, it is not known whether structural alterations of small arteries may also predict major cardiovascular events., Methods: Three hundred three subjects were included in the present study. There were 65 normotensive subjects, 111 patients with essential hypertension (33% of them with diabetes mellitus), 109 patients with secondary forms of hypertension, and 18 normotensive diabetic patients. Small-resistance arteries were dissected from subcutaneous fat biopsies and mounted on an isometric myograph, and the M:L was measured. Subjects were reevaluated after an average follow-up time of 6.9 years to assess the occurrence of cardio-cerebrovascular events., Results: Eleven subjects died of a fatal cardio-cerebrovascular event (FCE), 14 had a major, nonfatal cardiovascular event (stroke or myocardial infarction) (SMI), 23 had a minor cardiovascular event (MCE), and 255 had no cardiovascular event (NCE). A significant difference was observed in M:L and in event-free survival between patients with FCEs+SMIs+MCEs and those with NCE and between patients with FCEs+SMIs and those with NCE. Similar results were obtained by restricting the analysis to patients with essential hypertension., Conclusions: Structural alterations of small-resistance arteries may predict FCE and SMI. The prognostic role of small-resistance artery structure also applies to medium-risk patients with essential hypertension, at least when MCEs are included in the analysis.

We investigated the effects of MDL-100,240 in a transgenic rat model (TGRen2) of hypertension with severe cardiovascular damage (CVD) due to enhanced tissue synthesis of angiotensin II (Ang II). Male heterozygous TGRen2 rats (5 weeks old) were allocated to receive MDL-100,240, ramipril (RAM) or placebo (PLAC) for 4 weeks, during which blood pressure (BP) was measured. We then evaluated: 1) left ventricle (LV) and right ventricle (RV), brain, kidney and adrenals weight; 2) structural changes in the aorta and the mesenteric arterioles wall; 3) tension responses of segments of the aorta to phenylephrine, KCl, and endothelin-1; and 4) creatinine, aldosterone, atrial natriuretic peptide (ANP), and cyclic GMP (cGMP) plasma levels. Compared to PLAC, both MDL-100,240 and RAM significantly (P < .001) lowered BP (after 4 weeks: 255 +/- 15 mm Hg PLAC, v 174 +/- 6 MDL-100,240, v 166 +/- 5 RAM). They hindered LV hypertrophy (3.73 +/- 0.25 mg/g body weight (PLAC) v 2.71 +/- 0.22 (MDL-100,240) P < .001; v 2.36 +/- 0.2 (RAM), P < .001). MDL-100,240 also prevented aortic dilatation and hypertrophy of the mesenteric arterioles (media thickness, 25.3 +/- 0.5 microm PLAC, v 21.1 +/- 0.9 MDL-100,240, P < .007; v 20.2 +/- 1.5 RAM, P = .033) and lowered the tension responses to phenylephrine (P < .01), KCl (P < .01), and endothelin-1 (P < .001). Plasma aldosterone (710 +/- 153 pmol/L PLAC, v 237 +/- 61 MDL-100,240, v 180 +/- 22 RAM) and creatinine levels (0.69 +/- 0.33 mg/dL PLAC, v 0.41 +/- 0.02 MDL-100,240, v 0.41 +/- 0.04 RAM) were also decreased (P < or = .001). Compared to PLAC, plasma ANP levels were 11% and 2.4% higher in MDL-100,240 and RAM, respectively (both P = not significant); cGMP levels were unaffected. Thus, severe hypertension and related CVD were regressed by MDL-100,240, which resulted to be as effective as a full dosage of ramipril in TGRen2.

The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg received 8 weeks of verapamil sustained release (240 mg) and amlodipine (5 mg) in a prospective randomized, double blind, cross-over study, both after 4 weeks of placebo. The 24-h autonomic balance was measured by analysis of 24-h heart rate variability and short-term autonomic control of BP by baroreflex sensitivity measurements. Plasma norepinephrine was sampled at rest. Blood pressure was equally reduced from 153/100 mm Hg to 139/91 mm Hg with verapamil and 138/91 mm Hg with amlodipine, P = .50/.59. The low- to high-frequency ratio (LF/HF), reflecting sympathovagal balance, was higher with amlodipine than with verapamil (4.66 v 4.10; P = .001). Baroreflex function was improved by both treatments; however, baroreflex sensitivity (BRS) was significantly higher with verapamil than with amlodipine (8.47 v 8.06 msec/mm Hg; P = .01). Plasma norepinephrine (NE) level was higher with amlodipine than with verapamil (1.59 v 1.32 nmol/L; P < .0001). Amlodipine induces a shift in sympathovagal balance, as measured by heart rate variability indices and plasma NE, toward sympathetic predominance compared with vagal predominance with verapamil. Short-term autonomic control of BP, as assessed by BRS, is more effectively improved by verapamil than by amlodipine. These contrasting effects on autonomic function suggest that the nondihydropyridine calcium antagonist verapamil may have additional beneficial effects beyond lowering BP compared with the dihydropyridine amlodipine.

The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dysfunction, in human and experimental hypertension is still unclear. Moreover, the interrelationships between structural and functional vascular alterations are presently under debate. The aim of this study was to assess the arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as compared to age-matched normotensive Wistar-Kyoto rats (WKY). Seventeen SHR (4 to 12 weeks old) and 17 WKY were included in the study. Blood pressure was measured noninvasively. After killing the animals, relative left ventricular mass (RLVM) was calculated, and mesenteric arcades were dissected and mounted on a micromyograph. Functional and structural characteristics of the vessels were measured: media thickness (MT), media/lumen ratio (M/L), and wall tension in response to norepinephrine and acetylcholine. At 4 weeks of age, no difference in blood pressure and RLVM between SHR and WKY was detected, but MT and M/L of mesenteric small resistance arteries were significantly greater in SHR. An increased response to norepinephrine was observed in terms of wall tension, but not of active media stress at the two higher norepinephrine concentrations. No difference in the dose-response curve to acetylcholine between SHR and WKY was observed. At 8 and 12 weeks of age systolic blood pressure was significantly higher in SHR; RLVM, MT, and M/L were also higher at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously shown that transdermal nitroglycerin may induce an increase in the activity of the adrenergic and the renin-angiotensin-aldosterone systems (SRAA) in patients with chronic stable angina pectoris (SA); when the activation of these systems is more pronounced, the antianginal effect of this drug seems to be reduced. The aim of this study was to evaluate the antianginal efficacy of transdermal nitroglycerin administration (TTS-NG 10 mg.24 h-1) in combination with an ACE inhibitor without sulphydryl groups (BNZ, benazepril 10 mg b.i.d.) in respect to placebo, or to TTS-NG or BNZ administered as monotherapy. Twenty-four patients (21M, 3F) were admitted to this multicentre, randomized, double-blind, latin square, placebo-controlled study. Patients received all the treatments (placebo, TTS-NG, BNZ and BNZ + TTS-NG) each for one week; at the end of each week patients performed two exercise tests 2 and 22 h post-dosing. Two hours post-dosing, exercise duration at 1 mm ST depression was significantly increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05) treatments. Two hours post-dosing, exercise duration at peak exercise was also increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05); 22 h post-dosing the increase in exercise duration was significant only during TTS-NG + BNZ treatment (P < 0.05) in respect to placebo, but not during TTS-NG given alone. Rate-pressure product at 1 mm ST depression was significantly increased 2 h post-dosing during TTS-NG treatment (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Power spectral analysis of heart rate may provide useful information about cardiac neural activity. The aim of this study was to evaluate cardiac sympathetic and parasympathetic activity, as assessed by power spectral analysis of heart rate, in hypertensive patients before and after antihypertensive treatment. In 14 hypertensive patients and in 7 normotensive subjects 24 h Holter electrocardiogram monitoring was performed under basal conditions and after 6 months of treatment with nifedipine (n = 7) or enalapril (n = 7). Sequences of 512 RR intervals were taken for the evaluation of power spectral analysis (autoregressive method); absolute and normalized power spectral density of the peak at 0.10 Hz (low frequency peak: LF) and at 0.25 Hz (high frequency peak: HF), as well as their ratio (index of sympatovagal interaction: SVI) were calculated. Under basal conditions SVI was significantly decreased from daytime to nighttime in normotensives, while no change was observed in hypertensive patients. In all hypertensive patients a reduction of SVI during nighttime in respect to basal values was observed after treatment. SVI during nighttime was significantly reduced with both nifedipine and enalapril, while SVI during daytime was slightly increased during nifedipine treatment, and significantly reduced during enalapril treatment. Systolic and diastolic arterial pressure as well as left ventricular mass index were significantly reduced with both treatments. In conclusion, long term treatment with nifedipine or enalapril seems to be able to restore an impaired daytime to nighttime SVI modulation in hypertensive patients, even considering the potential limitations of power spectral analysis of heart rate.

It has been shown that in hypertensive patients the degree of target organ damage correlates more closely with average blood pressure as recorded by ambulatory monitoring (ABPM) throughout 24 h than with clinic blood pressure. We examined a group of 91 clinically healthy subjects, 23 normotensives and 68 hypertensives according to clinic blood pressure. Cardiac anatomy was investigated by echocardiography. As an index of arterial structural changes forearm minimal vascular resistance was calculated from mean arterial pressure and maximal postischemic blood flow, as assessed by venous occlusion plethysmography. The results were correlated to clinic blood pressure or ABPM values (measured by noninvasive ABPM ICR 5200, Spacelabs, Bellevue, CA). Left ventricular mass was correlated more closely with the average blood pressure recorded during 24 h, or during daytime or nighttime periods, than with clinic blood pressure. Minimal vascular resistance was also significantly correlated to ABPM values, but the correlation was similar to that observed with clinic blood pressure. Minimal vascular resistance was significantly correlated to blood pressure variability, as evaluated by the standard deviation of the mean. Minimal vascular resistance and left ventricular mass were higher in a subgroup of patients in whom blood pressure was not significantly reduced during the night. The results of this study confirm that elevated average ABPM values are associated to higher left ventricular mass; in addition, they suggest that increased blood pressure variability may be associated with vascular structural changes, as evaluated by minimal vascular resistance. It remains to be clarified whether cardiac hypertrophy and/or vascular structural changes are a cause or consequence of increased blood pressure values and variability.

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

The possible involvement of peripheral dopaminergic mechanisms in the action of atrial natriuretic peptides was investigated in 10 subjects by administering 200 micrograms h-ANP 99-126 intravenously for 30 min during treatment with 50 mg carbidopa, a peripheral inhibitor of dopamine synthesis, every 8 h, or during placebo. Atrial natriuretic peptide (ANP) infusion during placebo was associated with a significant increase of diuresis, natriuresis, kaliuresis, urinary noradrenaline, and dopamine excretion. Plasma aldosterone significantly decreased. Blood pressure was slightly reduced. The administration of carbidopa significantly reduced urinary dopamine excretion but did not modify natriuresis, diuresis, indexes of adrenergic and renin-aldosterone system activity, blood pressure, or heart rate, both in basal conditions and in response to ANP infusion. We conclude that the effects of exogenous ANP administration are independent from dopaminergic mechanisms that involve the synthesis of dopamine outside the central nervous system, particularly in the kidney.

Morbidity and mortality are higher in hypertensive patients who have already developed cardiovascular complications. Several prospective epidemiological and clinical studies have indicated that regression of cardiovascular alterations, preferably when still at an initial stage, is a desirable goal in the treatment of hypertension. Clinical assessment of cardiac hypertrophy may be precisely obtained with echocardiography. Structural vascular changes may be evaluated indirectly in man by measuring minimal vascular resistance from maximal blood flow and arterial pressure. The results of a large number of studies have indicated that in hypertensive patients a significant regression of cardiovascular structural changes may be obtained with several antihypertensive drugs, but they have not yet established whether a complete "normalization" may be really obtained. Further studies are needed to identify factors that modulate regression of cardiac and vascular smooth muscle hypertrophy. Most important, it still remains to be clarified whether regression of cardiovascular structural changes in hypertensives significantly improves prognosis per se independently from blood pressure reduction.