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Alterations in microcirculation play a crucial role in the pathogenesis of cardiovascular and metabolic disorders such as obesity and hypertension. The small resistance arteries of these patients show a typical remodeling, as indicated by an increase of media or total wall thickness to lumen diameter ratio that impairs organ flow reserve. The majority of blood vessels are surrounded by a fat depot which is termed perivascular adipose tissue (PVAT). In recent years, data from several studies have indicated that PVAT is an endocrine organ that can produce a variety of adipokines and cytokines, which may participate in the regulation of vascular tone, and the secretory profile varies with adipocyte phenotype and disease status. The PVAT of lean humans largely secretes the vasodilator adiponectin, which will act in a paracrine fashion to reduce peripheral resistance and improve nutrient uptake into tissues, thereby protecting against the development of hypertension and diabetes. In obesity, PVAT becomes enlarged and inflamed, and the bioavailability of adiponectin is reduced. The inevitable consequence is a rise in peripheral resistance with higher blood pressure. The interrelationship between obesity and hypertension could be explained, at least in part, by a cross-talk between microcirculation and PVAT. In this article, we propose an integrated pathophysiological approach of this relationship, in order to better clarify its role in obesity and hypertension, as the basis for effective and specific prevention and treatment., Competing Interests: Disclosures None.

It has been suggested that measurement of unattended or automated oscillatory blood pressure (BP) values may provide advantages over conventional BP measurement. Some international guidelines now suggest automated oscillatory BP as the preferred approach for measuring BP. Data on the relationship between automated oscillatory BP and cardiovascular events are much less solid as compared to those obtained with the standard approach; preliminary data suggested that automated oscillatory BP might be more strictly correlated with organ damage. The aim of our study was to evaluate the relationship between attended or unattended BP and organ damage in 564 subjects undergoing an echocardiogram and carotid ultrasound at an European Society of Hypertension Excellence Center.Both unattended BP (patient alone in the room, an oscillometric device programmed to perform 3 BP measurements, at 1-minute intervals, after 5 minutes) and attended BP were measured with the same device, on the same day of the ultrasonographic examination, in random order. In 564 patients (age 61±15 years, 41% female 78% hypertensives) systolic unattended BP was lower as compared with attended BP (128.0±15.5 versus 134.5±19.9 mm Hg). Left ventricular mass index was similarly correlated with attended and unattended systolic BP ( r=0.205 and r=0.194, respectively). Carotid intima-media thickness was also significantly correlated with both attended and unattended systolic BP (mean max intima-media thickness: r=0.206 and r=0.194, respectively, P<0.0001). The differences between correlations were not statistically significant. Our results suggest that attended and unattended BP values are similarly related with hypertensive organ damage.

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus., (© 2014 American Heart Association, Inc.)

Wall-to-lumen ratio of retinal arterioles might serve as an in vivo parameter of vascular damage. We analyzed the impact of brachial clinic blood pressure (BP), of central BP, and of 24-hour BP on wall-to-lumen ratio (WLR) of retinal arterioles. In 295 subjects (147 men; age range, 22-72 years; mean age, 54±7 years), WLR of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. In addition, clinic and 24-hour BP values were measured. Central hemodynamics was assessed by pulse wave analysis. In treated patients with essential hypertension (n=100), a higher WLR (0.29±0.18 versus 0.23±0.13; P=0.009) was observed in comparison with normotensive individuals (n=119); no significant differences were observed between treated and untreated hypertensive patients (0.29±0.18 versus 0.28±0.18; P=0.7). WLR of retinal arterioles was significantly related to clinic systolic (r=0.18; P=0.002) and pulse pressure (r=0.20; P=0.001), to 24-hour systolic (r=0.25; P=0.0001) and pulse pressure (r=0.17; P=0.005), and to central systolic (r=0.16; P=0.006) and pulse pressure (r=0.18; P=0.002). Multiple regression analysis revealed that only mean systolic 24-hour BP was independently associated with an increased WLR of retinal arterioles. In this large group of hypertensive patients and normotensive individuals, 24-hour systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.

The possible relationships between indicators of small resistance artery structure and of arterial stiffness and central hemodynamics have not yet been evaluated. Aim of this study was to assess the relationship between indicators of large arteries stiffness, including carotido-femoral pulse wave velocity and of vascular alterations in small resistance arteries (media/lumen ratio, M/L) in patients with primary and secondary hypertension. In 73 patients (mean age, 53±14 years, 34 females, 25 with type 2 diabetes mellitus, 18 never treated) with essential (n=37) and secondary (n=36) hypertension, carotido-femoral pulse wave velocity was measured. In all patients, small resistance arteries were dissected from subcutaneous fat biopsies and mounted on an isometric myograph, for the measurement of the M/L. Pulse wave analysis was performed in 67 patients. M/L ratio was significantly related to brachial systolic blood pressure and pulse pressure (r=0.36 and 0.31, P<0.001, respectively) and to central systolic and pulse pressure (r=0.44 and 0.42, P<0.001, respectively). A positive correlation was observed between M/L ratio and carotido-femoral pulse wave velocity (r=0.45; P<0.001); this correlation remained statistically significant after adjustment for age and mean blood pressure. M/L ratio was also associated to aortic augmentation index (r=0.33; P=0.008), and this correlations remained statistically significant after adjustment for potential confounders. In hypertensive patients, the presence of structural alterations of small resistance arteries may be associated with the increase in large arteries stiffness and possibly contribute to an increase in central pressure by increasing the magnitude of wave reflections.

It was suggested that oxidative stress has a key role in the development of endothelial dysfunction, as well as microvascular structural alterations. Therefore, we have investigated 2 substances with antioxidant properties: melatonin and Pycnogenol. We treated 7 spontaneously hypertensive rats (SHRs) with melatonin and 7 with Pycnogenol for 6 weeks. We compared results obtained with those observed in 7 SHRs and 7 Wistar-Kyoto normotensive control rats kept untreated. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and a concentration-response curve to acetylcholine was performed. Aortic contents of metalloproteinase 2, Bax, inducible NO synthase, and cyclooxygenase 2 were evaluated, together with the aortic content of total collagen and collagen subtypes and apoptosis rate. A small reduction in systolic blood pressure was observed. A significant improvement in mesenteric small resistance artery structure and endothelial function was observed in rats treated with Pycnogenol and melatonin. Total aortic collagen content was significantly greater in untreated SHRs compared with Wistar-Kyoto control rats, whereas a full normalization was observed in treated rats. Apoptosis rate was increased in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; an even more pronounced increase was observed in treated rats. Bax and metalloproteinase 2 expressions changed accordingly. Cyclooxygenase 2 and inducible NO synthase were more expressed in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; this pattern was normalized by both treatments. In conclusion, our data suggest that treatment with Pycnogenol and melatonin may protect the vasculature, partly independent of blood pressure reduction, probably through their antioxidant effects.

Assessment of appropriateness of left ventricular mass (LVM) for a given workload may better stratify hypertensive patients. Inappropriate LVM may reflect the interaction of genetic and neurohumoral factors other than blood pressure playing a significant role in myocardial growth. Primary aldosteronism (PA) represents a clinical model useful in assessing the effect of aldosterone increase on LVM. The aim of this study was to evaluate the inappropriateness of LVM in patients with PA. In 125 patients with PA (54 females; adrenal hyperplasia in 73 and adenoma in 52 patients) and in 125 age-, sex-, and blood pressure-matched, essential hypertensive patients, echocardiography was performed. The appropriateness of LVM was calculated by the ratio of observed LVM to the predicted value using a reference equation. In all of the subjects plasma renin activity and aldosterone, as well as clinic and 24-hour blood pressure, were measured. The prevalence of inappropriate LVM was greater in patients with traditionally defined left ventricular hypertrophy (70% and 44%, respectively; P=0.02) but also in patients without left ventricular hypertrophy (17% and 9%, respectively; P=0.085). In PA patients, a correlation was observed between the ratio of observed:predicted LVM and the ratio of aldosterone:plasma renin activity levels (r=0.29; P=0.003) or the postinfusion aldosterone concentration (r=0.44; P=0.004; n=42). In conclusion, in patients with PA, the prevalence of inappropriate LVM is increased, even in the absence of traditionally defined left ventricular hypertrophy. The increase in aldosterone levels could contribute to the increase of LV mass exceeding the amount needed to compensate hemodynamic load.

Remodeling of the resistance arteries is a hallmark of arterial hypertension and predicts cardiovascular events, but it was unknown whether it could also predict the blood pressure response to adrenalectomy of patients with an aldosterone-producing adenoma. Therefore, we investigated the outcome of adrenalectomy as a function of vascular remodeling in the context of the preoperative features of aldosterone-producing adenoma patients. At 2 referral centers for hypertension, we prospectively measured the media:lumen ratio of small arteries from fat tissue of 50 consecutive aldosterone-producing adenoma patients treated with adrenalectomy. The blood pressure response to adrenalectomy was assessed by considering the blood pressure values and the number and dosages of antihypertensive medications. Adrenalectomy significantly (P<0.001) lowered plasma aldosterone (from 27.3+/-4.9 ng/dL to 8.3+/-11.2 ng/dL), the aldosterone:renin ratio (from 117+/-35 to 11+/-2), and blood pressure (from 163+/-22/98+/-2 mm Hg to 133+/-2/84+/-1 mm Hg), even despite a reduction (from 141+/-14 to 100+/-15; P=0.02) of the score of antihypertensive treatment. It provided cure of hypertension in 30% of the aldosterone-producing adenoma patients, normotension with less antihypertensive therapy in 52%, and improved blood pressure control in the rest. The media:lumen ratio and the known duration of hypertension significantly predicted the blood pressure response to adrenalectomy at univariate and multivariate analyses. Because a long duration of hypertension and/or the presence of vascular remodeling imply lower chances of blood pressure normalization at long-term follow-up postadrenalectomy, these findings emphasize the importance of an early diagnosis of aldosterone-producing adenoma.

We performed a prospective head-to-head comparison of the accuracy of the captopril test (CAPT) and the saline infusion test (SAL) for confirming primary aldosteronism due to an aldosterone-producing adenoma (APA) in patients with different sodium intake. A total of 317 (26.9%) of the 1125 patients screened in the Primary Aldosteronism Prevalence in Italy Study underwent both CAPT and SAL. They were composed of the patients with a high aldosterone/renin ratio baseline and 1 every 4 patients without such criterion. The accuracy of post-CAPT or post-SAL plasma aldosterone values for diagnosing APA was estimated with the area under the receiver operator characteristics curves. Primary aldosteronism was found in 120 patients, of which 46 had an APA. No untoward effect occurred with either test. The area under the receiver operator characteristics curve of plasma aldosterone for both tests was higher (P<0.0001) than that under the diagonal, but the between-test difference was borderline significant (P=0.054). The optimal aldosterone cutoff value for identifying APA was 13.9 and 6.75 ng/dL for the CAPT and SAL, respectively. Even at these cutoffs, sensitivity and specificity were moderate because of overlap of values between patients with and without APA. When examined in relation to sodium intake, the accuracy of the SAL surpassed that of the CAPT in the patients with a sodium intake 7.6 g per day, the SAL offers no advantage over the easier-to-perform CAPT.

Inappropriate left ventricular mass (LVM; ie, the value of LVM exceeding individual needs to compensate hemodynamic load) predicts the risk of cardiovascular (CV) events, independent of risk factors, either in the presence or in the absence of traditionally defined LV hypertrophy. The relation between changes in appropriateness of LVM during antihypertensive treatment and subsequent prognosis was evaluated in 436 prospectively identified uncomplicated hypertensive subjects, with a baseline and follow-up standard clinical evaluation, laboratory examinations, and echocardiogram (last examination: 6+/-3 years apart), followed for additional 4.5+/-2.5 years. The appropriateness of LVM to cardiac workload was calculated by the ratio of observed LVM to the value predicted for individual sex, height, and stroke work at rest. At baseline, low or appropriate LVM (

Left ventricular (LV) mass and geometry predict risk for cardiovascular events in hypertension. Regression of LV hypertrophy (LVH) may imply an important prognostic significance. The relation between changes in LV geometry during antihypertensive treatment and subsequent prognosis has not yet been determined. A total of 436 prospectively identified uncomplicated hypertensive subjects with a baseline and follow-up echocardiogram (last examination 72+/-38 months apart) were followed for an additional 42+/-16 months. Their family doctor gave antihypertensive treatment. After the last follow-up echocardiogram, a first cardiovascular event occurred in 71 patients. Persistence of LVH from baseline to follow-up was confirmed as an independent predictor of cardiovascular events. Cardiovascular morbidity and mortality were significantly greater in patients with concentric (relative wall thickness > or =0.44) than in those with eccentric geometry (relative wall thickness <0.44) in patients presenting with LVH (P=0.002) and in those without LVH (P=0.002) at the follow-up echocardiogram. The incidence of cardiovascular events progressively increased from the first to the third tertile of LV mass index at follow-up (partition values 91 and 117 g/m2), but for a similar value of LV mass index it was significantly greater in those with concentric geometry (OR: 4.07; 95% CI: 1.49 to 11.14; P=0.004 in the second tertile; OR: 3.45; 95% CI: 1.62 to 7.32; P=0.001 in the third tertile; P<0.0001 in concentric versus eccentric geometry). Persistence or development of concentric geometry during follow-up may have additional prognostic significance in hypertensive patients with and without LVH.

Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.

Previous studies suggest that variants of the beta(2)-adrenergic receptor (ADRB2) may differently affect functional responses to adrenergic stimulation, thereby possibly modulating cardiovascular and metabolic phenotypes. We examined the hypothesis that G/R16 and Q/E27 polymorphism of ADRB2, or their haplotypes, may modulate blood pressure, cardiovascular structure, and function or metabolic cardiovascular risk factors in the general population. We examined a random sample of the general population (n=571; age, 35 to 64 years). Neither clinic nor 24-hour ambulatory blood pressure was significantly associated with ADRB2 genotypes in the overall population. Cardiac structure and function were also not influenced by ADRB2 polymorphism. After adjustment for potential confounders, association of the R16 allele with higher systolic blood pressure was observed in the subgroup of younger people (below age of 50 years). Haplotype analysis showed that higher blood pressure values were more specifically associated with the presence of R16-Q27. Younger people carrying the R16-Q27 haplotype also showed a trend toward lower heart rate, higher BMI, lower glycemia, and higher trygliceridemia, which is consistent with the hypothesis of a genetic predisposition to reduced cardiovascular and metabolic response to ADRB2 stimulation. This study does not provide evidence of a major role of ADRB2 gene variability in blood pressure modulation. However, association of ADRB2 polymorphism with cardiovascular and metabolic effects can be observed in younger subjects, before the development of age-related decline of ADRB2-mediated activity. Our study emphasizes the necessity of taking into account (patho)-physiological changes related to aging (in this case, decreased efficiency of ADRB2 signaling) when analyzing phenotypic effects of genetic variants.

off aim of our study was to evaluate the effect of antihypertensive treatment on flow-mediated dilation (FMD)of a large artery, a noninvasive estimate of endothelial function, in hypertensive patients. In 78 consecutive hypertensive patients (40%men; age range, 42 to 67 years) we measured by a high-resolution ultrasound system the changes of brachial artery diameter during reactive hyperemia and after sublingual glyceryl trinitrate (400 microg); brachial artery flow velocity was measured by pulsed Doppler. The results of 2 studies are reported. In the first study, this procedure was repeated in 58 patients after 6 and 12 months of treatment with a combination of antihypertensive drugs; in a second study, the FMD was assessed in 20 patients after 2 months of monotherapy with either nifedipine or hydrochlorothiazide. In the first study, FMD was significantly increased after treatment compared with baseline (from 3.1+/-3% at baseline to 6.5+/-4.5% at 6 months and to 8.12+/-4. 6% at 12 months; P<0.001 by ANOVA), concomitant with blood pressure reduction (from 162+/-24/102+/-13 mm Hg to 141+/-12/89+/-6 mm Hg and to 141+/-9/89+/-6 mm Hg; P<0.001 by ANOVA); significant changes of endothelium-independent dilation were also observed, but only after 12 months of treatment (from 14.2+/-4.8 at baseline to 15.5+/-4.7 at 6 months and 16.8+/-5.9% at 12 months; P=0.03 by ANOVA). In the second study, FMD was significantly increased during nifedipine treatment as compared with baseline (from 5+/-6.18% at baseline to 9. 45+/-3.94%, P<0.001), while it did not change in patients receiving hydrochlorothiazide (from 5.15+/-5.28% at baseline to 4.69+/-4.34%, NS). No significant changes of endothelium-independent dilation were observed with both drugs (from 17.10+/-2.4% to 18.14+/-3.76% and from 18.73+/-4.07% to 17.46+/-4.27% during nifedipine and hydrochlorothiazide, respectively, NS). Thus, in essential hypertensive patients an improvement of the impaired FMD of the brachial artery, evaluated by noninvasive ultrasound, may be observed after long-term, effective blood pressure reduction, suggesting a beneficial effect of antihypertensive treatment on endothelial function. It seems that beyond blood pressure control, a calcium antagonist may be more effective than a diuretic in this respect.

We evaluated the effects on cardiovascular structure of the angiotensin-converting enzyme (ACE) inhibitor enalapril and of the angiotensin II receptor blocker losartan, administered either at hypotensive or nonhypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg x kg(-1) x d(-1)) enalapril, low-dose (0.5 mg x kg(-1) x d(-1)) losartan, high-dose (25 mg x kg(-1) x d(-1)) enalapril, or high-dose (15 mg x kg(-1) x d(-1)) losartan. Untreated WKY and SHR were also studied. Rats were killed at 13 weeks of age, and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness and lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbiased "disector" method. Systolic blood pressure was significantly reduced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (P<0.05). In the high-dose enalapril and losartan groups, there were similar reductions in relative left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of the structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodeling of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despite the smaller hypotensive effect.

The aim of our study was to evaluate the relationships between endothelial function, small resistance artery structure, and blood pressure in patients with primary or secondary hypertension. Sixty subjects were included in the study: 9 patients with pheochromocytoma, 10 with primary aldosteronism, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotensive subjects who served as controls. Clinic and 24-hour ambulatory blood pressure (ABPM) were evaluated. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph and the media/lumen ratio was calculated. A dose-response curve to acetylcholine was performed at cumulative concentrations from 10(-9) to 10(-5) mol/L. The vasodilator response to acetylcholine was similarly impaired in the four groups of hypertensive patients (ANOVA P<.05 versus normotensive controls), without any significant difference among them. In subcutaneous small arteries of patients with either primary aldosteronism or renovascular hypertension, a marked increase in media:lumen ratio was observed, while in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in essential hypertension. No significant correlation between media-lumen ratio or clinic blood pressure and maximum acetylcholine-induced vasodilatation was observed. On the contrary, a significant, albeit not very close, correlation between ABPM values and maximum acetylcholine-induced vasodilatation was observed (r=34, P<.05 with 24-hour systolic blood pressure, r=0.36, P<.05 with 24-hour diastolic blood pressure). In conclusion, endothelial dysfunction seems to be independent from the degree of vascular structural alterations and from the etiology of hypertension, and it is probably more linked to the hemodynamic load.

The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.

It has been proposed that several neurohumoral factors may be involved in the genesis of vascular structural changes (remodeling or hypertrophy) frequently observed in essential hypertension. Therefore, in this study we investigated vascular structural alterations of subcutaneous small resistance arteries in patients with secondary forms of hypertension. The study included 70 participants: 11 with pheochromocytoma, 13 with primary aldosteronism, and 17 with renovascular hypertension; 13 normotensive subjects and 16 patients with essential hypertension served as controls. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph, and media-lumen ratio, media thickness, remodeling index, and growth index were evaluated. Endothelial function was evaluated according to the dose-response curve to acetylcholine. In patients with either primary aldosteronism or renovascular hypertension, a marked increase in media-lumen ratio was observed, whereas in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in patients with essential hypertension. The increase in media-lumen ratio in patients with essential hypertension and with pheochromocytoma was mainly due to vascular remodeling (remodeling index, 93% to 94%), whereas in patients with renovascular hypertension, there was vascular growth (remodeling index, 70%; growth index, 53%). Patients with primary aldosteronism had an intermediate pattern compared with the other two forms of secondary hypertension. An evident impairment of endothelial function was observed in all four hypertensive groups. In conclusion, the renin-angiotensin-aldosterone system seems to be more powerful than the adrenergic system in inducing vascular growth.

The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m2 in men and greater than 110 g/m2 in women were considered abnormal, indicating the presence of left ventricular hypertrophy. Blood pressure (BP) was measured in the clinic setting with a mercury sphygmomanometer and by 24-hour noninvasive ambulatory monitoring. Hypertension was defined as a sustained systolic BP greater than or equal to 160 mm Hg and/or diastolic BP increase greater than or equal to 95 mm Hg. The study population consisted of 225 subjects (107 women and 118 men) 48 to 64 years old. Prevalence of intima-media thickening (intima-media thickness > 1 mm) was 11% in normotensive subjects and 44% in hypertensive subjects. The presence of plaque (wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall, usually > 2 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r = .20 and r = .19, respectively; P < .01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P < .01). However, in the multivariate analysis, body mass index (P = .027), sex (P < .001), and 24-hour mean BP (P = .025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P < .001), cigarette smoking (P = .009), serum cholesterol (P = .025), serum glucose (P = .038), and nighttime systolic BP (P = .006). Logistic regression analysis confirmed the association between the presence of plaque and age (P < .001), nighttime systolic BP (P < .05), and cigarette smoking (P < .05); a negative association between plaque and the decrease in mean systolic BP daytime to nighttime was also observed (P < .001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different.

In this study we evaluated the delayed effects of a calcium entry blocker on blood pressure and on vascular structural and functional alterations in mesenteric resistance arteries of spontaneously hypertensive rats (SHR). The calcium entry blocker nitrendipine was administered (30 mg/kg per day) according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 12), and in a third group from 4 to 12 weeks of age (n = 12). Twelve untreated SHR and 12 untreated Wistar-Kyoto rats served as controls. Half the animals of each group were killed at 13 weeks, and the remaining were killed at 38 weeks. After death, relative left ventricular mass was calculated. Vascular morphology and function (responses to norepinephrine and acetylcholine) in mesenteric small arteries were then assessed using a micromyographic technique. Nitrendipine treatment delayed the development of hypertension and determined the regression of structural alterations of mesenteric resistance arteries in SHR. These favorable effects were maintained for several weeks after treatment withdrawal, provided that treatment was started at 4 weeks of age. Considering the functional alterations of mesenteric arteries in SHR (responses to norepinephrine and acetylcholine), nitrendipine treatment determined an improvement of both these dysfunctions as long as reductions of the media-to-lumen ratio and blood pressure, respectively, were maintained.