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Objective: Microvascular structural alterations may be considered an important form of hypertension-mediated organ damage. An increased media-to-lumen ratio of subcutaneous small arteries evaluated with locally invasive techniques (micromyography) predicts the development of cardiovascular (CV) events. However, it is not known whether retinal arteriole structural alterations evaluated with a noninvasive approach (Adaptive Optics) may have a prognostic significance., Design and Methods: Two-hundred and thirty-seven subjects (mean age 58.7 ± 16.1 years, age range 13-89 years; 116 males) were included in the study: 65 normotensive subjects (27.4 %) and 172 patients with essential hypertension or primary aldosteronism (72.6 %). All subjects underwent a non-invasive evaluation of retinal arteriolar wall-to-lumen ratio (WLR) by Adaptive Optics. Subjects were re-evaluated after an average follow-up time of 4.55 years in order to assess the occurrence of clinical events (non CV and/or CV death or events)., Results: Fifty-four events occurred in the study population:26 were cardio-cerebrovascular events (ischemic or hemorragic stroke, atrial fibrillation, heart failure, coronary artery disease, peripheral artery disease, cardiac valvular disease) while the remaining were deaths for any cause, or neoplastic diseases. Subjects with events were older and had a WLR of retinal arterioles significantly greater than those without events. The event-free survival was significantly worse in those with a baseline WLR above the median value of the population (0.28) according to Kaplan-Mayer survival curves and multivariate analysis (Cox's proportional hazard model). The evidence was confirmed after restricting the analysis to CV events., Conclusions: Structural alterations of retinal arterioles evaluated by Adaptive Optics may predict total and CV events., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The evaluation of microvascular alterations might provide clinically useful information for patients with an increased cardiovascular (CV) risk, such as those with rheumatoid arthritis (RA), being the small artery remodeling the earliest form of target organ damage in primary CV diseases, such as arterial hypertension. The evaluation of retinal arterioles is a non-invasive technique aimed to identify an early microvascular damage, represented by the increase of the wall-to-lumen ratio (WLR) index. Abatacept (ABA), a T-cell co-stimulator blocker, is used to treat RA. A CV protective action was hypothesized for its peculiar mechanism of action in the modulation of T-cells, potentially involved in the pathogenesis of CV comorbidity. The study aimed to non-invasively investigate morphological characteristics of retinal arterioles in a cohort of RA patients treated with ABA., Materials and Methods: Seventeen RA patients [median (25th-75thpercentile) age = 58 (48-64) years, baseline 28-joint Disease Activity Score DAS28-C-reactive protein (DAS28-CRP) = 4.4 (3.9-4.6), body mass index (BMI) = 24.2 (23.4-26) kg/m 2 , rheumatoid factor positive:52.9%, anti-citrullinated peptide autoantibodies positive:76.5%] without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by the adaptive optics imaging system of retinal arterioles before and every 6 months of therapy with ABA (T0, T6 and T12). Office blood pressure evaluation, 24-h ambulatory blood pressure monitoring and tissue-doppler echocardiography were also performed., Results: A progressive significant reduction of the WLR of retinal arterioles was observed [T0 = 0.28 (0.25-0.30), T6 = 0.27 (0.24-0.31), T12 = 0.23 (0.23-0.26); p T0 vs. T6 = 0.414; p T6 vs. T12 = 0.02; p T0 vs. T12 = 0.009], without significant variations in other parameters. The T0-T12 reduction of WLR was correlated with that of DAS28-CRP (r:0.789; p = 0.005). Moreover, a significant reduction of diastolic office blood pressure and a trend for reduction of daily pressure measured by ambulatory monitoring were observed., Conclusion: In a cohort of RA patients without known CV risk factors, a reduction of retinal microvascular alterations was demonstrated after treatment for 12 months with ABA, in parallel with the reduction of disease activity. These results might suggest the possibility of microvascular abnormalities regression induced by the immune system modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piantoni, Regola, Angeli, Caproli, Trovati, Tomasi, Chiarini, Rossini, Rosei, De Ciuceis, Franceschini, Muiesan, Rizzoni and Airò.)

Background: Acute SarsCov2 infection is associated with endothelial dysfunction and 'endothelitis', which might explain systemic microvascular impairment. The presence of endothelial damage may promote vasoconstriction with organ ischemia, inflammation, tissue oedema and a procoagulant state resulting in an increase in the incidence of cardiovascular and cerebrovascular events. Microvascular thrombosis has been demonstrated in postmortem autopsy of COVID-19 patients; however, few data are available about skin capillary alterations in these patients., Materials and Methods: We evaluated skin microvascular alteration in 22 patients admitted to our hospital with SarsCov2 infection. Capillary density was evaluated by capillaroscopy in the nailfold and the dorsum of the finger in the acute phase of the disease. Capillaroscopy was repeated after 3 months (recovery phase). In addition, blood chemistry parameters and inflammatory markers were obtained during acute infection and at the recovery after 3 months., Results: Patients with COVID-19 showed skin microvascular complications, such as thrombosis, microhaemorrhages and neoangiogenesis, which were not detected after 3 months from the discharge. A significant reduction of capillary density in the dorsum was observed after 3 months from the acute infection (97.2 ± 5.3 vs. 75.81 ± 3.9 n/mm 2P  < 0.05). A significant inverse correlation between C-reactive protein and capillary density was observed in patients with acute SarsCov2 infection ( r  = 0.44, P  < 0.05). Conversely a direct correlation between capillary density during the acute phase and lymphocyte number was detected ( r  = 0.49, P  < 0.05)., Conclusion: This is the first in-vivo evidence of skin capillary thrombosis, microhaemorrhages and angiogenesis in patients with acute SarsCov2 infection, which disappeared after 3 months, supporting the presence of endothelial dysfunction and inflammation. Capillary alterations might reflect systemic vascular effects of viral infection., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: At present, few data are available on the prognosis of hypertensive emergencies and urgencies admitted to emergency departments., Aim: The aim of our study was to evaluate the incidence of total and cardiovascular events during follow-up in hypertensive patients admitted to the emergency departments of Brescia Hospital (Northern Italy) with hypertensive emergencies or urgencies from 1 January to 31 December 2015., Methods: Medical records of patients aged more than 18 years, admitted to the emergency department with SBP values at least 180 mmHg (SBP) and/or DBP values at least 120 mmHg (DBP) were collected and analysed (18% of patients were classified as 'hypertensive emergency' and 82% as 'hypertensive urgency'). Data in 895 patients (385 men and 510 women, mean age 70. 5 ± 15 years) were analysed; the mean duration of follow-up after admission to the emergency department was 12 ± 5 months., Results: During the follow-up, 96 cardiovascular events (28 fatal) occurred (20 cardiac events, 30 cerebrovascular events, 26 hospital admission for heart failure, 20 cases of new onset kidney disease). In 40 patients (4.5%), a new episode of acute blood pressure rise with referral to the emergency department was recorded. Cardiovascular mortality and morbidity were greater in patients with a previous hypertensive emergency (14.5 vs. 4.5% in patients with hypertensive emergency and urgency, respectively, chi-square, P < 0.0001). Similar results were obtained when the occurrence of cerebrovascular or renal events were considered separately., Conclusion: Admission to the emergency department for hypertensive emergencies and urgencies identifies hypertensive patients at increased risk for fatal and nonfatal cardiovascular events. Our findings add some new finding suggesting that further research in this field should be improved aiming to define, prevent, treat and follow hypertensive urgencies and emergencies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: to analyze the presence of cardiac and vascular preclinical damage in premenopausal women with systemic lupus erythematosus (SLE) and controls, matched for demographic characteristics and for other cardiovascular risk factors., Methods: 33 women (mean age 32 ± 7 years) with SLE clinically stable (SLEDAI Score 2.5 ± +1.5) and 33 controls, matched (MC) for sex, age, body mass index (BMI), clinic blood pressure (BP) and antihypertensive treatment (if present) underwent: 24-h BP monitoring, echocardiography with tissue Doppler analysis for left ventricular (LV) structure, systolic and diastolic function, echo-tracking carotid ultrasound for intima-media thickness (IMT) and carotid distensibility measurement, and pulse wave velocity measurement for aortic stiffness (PWV)., Results: by definition no difference was observed for age, sex, BMI and clinic BP values; Framingham risk score was low in SLE and MC (1.3 ± 2.7 vs 1.5 ± 2.3%, p = ns). 24-h BP was similar in SLE and in MC. Systolic function parameters, including LV longitudinal systolic function, an early index of LV systolic dysfunction, were reduced in SLE as compared to MC. Carotid IMT and carotid and aortic stiffness parameters were not different in SLE and MC. At multivariate regression analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients., Conclusions: in young patients with SLE and low activity index of the disease, we did not observe significant vascular alterations as compared to controls with similar CV risk. The early LV systolic impairment observed in SLE patients needs confirmation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: An increasing attention is given to emergency departments (EDs) admissions for an acute and severe rise in blood pressure (BP). Data on epidemiology and treatment of hypertensive emergencies and urgencies admitted to ED are still limited. The aim of our study was to evaluate the prevalence, clinical presentation and treatment of patients admitted for hypertensive emergencies or hypertensive urgencies., Methods: Medical records of consecutive patients aged at least 18 years, admitted to the ED of the Spedali Civili in Brescia in 2008 and in 2015 and presenting with SBP at least 180 mmHg and/or DBP at least 120 mmHg were prospectively collected and analysed., Results: The prevalence of patients admitted with acute BP rise was 2.0% (n = 1551, age 70 ± 14 years) in 2008 and 1.75% (n = 1214, age 69.7 ± 15 years) in 2015. According to the clinical presentation and the presence of acute organ damage, patients were defined hypertensive emergencies (20.4 and 15.4%, respectively, in 2008 and 2015) or as hypertensive urgencies (79.6 and 84.5%, respectively, in 2008 and 2015). SBP and DBP values were higher in patients with emergencies than in those with urgencies (BP 193 ± 15/102 ± 15 vs. 189 ± 13/96 ± 13 mmHg in 2008 and 192 ± 17/98 ± 15 vs. 189 ± 12/94 ± 15 mmHg in 2015, P < 0.001 for both).Among hypertensive emergencies, the different forms of organ damage were 25% acute coronary syndromes and 1% aortic dissection in both periods, 34 and 38% acute heart failure, 40 and 37% stroke., Conclusion: Admission to the ED for hypertensive emergencies and hypertensive urgencies is still high. Diagnosis and treatment are still not appropriate and require the rapid application of recently published guidelines.

An adequate cardiovascular (CV) prevention strategy in women should consider the acknowledgement of sex-specific risk factors, such as hypertension in pregnancy, the concomitant presence of autoimmune diseases and the benefit of evaluating subclinical organ damage and treating hypertension. In accordance to current guidelines, the diagnostic approach does not differ between men and women, although the cardiac response to pressure overload may suggest greater sensitivity in women, and may vary according to age, ethnic background and obesity, that potentiates the effect of hypertension on left ventricular (LV) hypertrophy. Several studies have observed peculiar abnormalities in LV systolic and diastolic function according to gender. The possible mechanisms that influence a different cardiac adaptation to chronic pressure overload in men and women are not fully understood, although hormonal status, and in particular the lack of estrogen effects after menopause may contribute to the cardiovascular adaptation response to increased afterload. The increase in LV mass in response to chronic pressure overload is associated with higher LV ejection fraction in women than in men and LV torsion is maintained with aging in women but not in men. Interstitial fibrosis may reduce circumferential shortening and early diastolic strain rate, in the presence of a preserved ejection fraction in women, favoring the development of heart failure with preserved ejection fraction. Changes in aortic stiffness with aging may influence cardiac structural and functional changes. Isolated systolic hypertension reflects an increase in aortic stiffness, is frequent in women and may be associated to a greater development of concentric LVH. The regression of hypertensive LVH is more difficult in women, and residual hypertrophy is more common in women than in men despite effective antihypertensive treatment and blood pressure control. Carotid atherosclerosis has been extensively investigated in men and women, showing that women usually develop carotid plaques after menopause, with smaller and less unstable plaques; however large and/or a hypoechogenic plaques are more strictly related to cerebrovascular events in women than in men. More advanced abnormalities in the subcutaneous microcirculation have been recently observed, and well translate in the evidence of more prevalent coronary microcirculation involvement in women ischemic heart disease. The prevalence of albuminuria and of reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73) are respectively lower and higher in postmenopausal women than in men. Experimental data suggest the possible involvement of renin-angiotensin-aldosterone system and of T regulatory lymphocytes to this regard.

In European countries and in the USA, hypertension represents an important risk factor for cardiovascular diseases (CVD) in men and women. Women do not perceive CVD as an important health problem, despite the evidence that women are more at risk to die from hypertension-related CVD than men. A correct prevention strategy should more widely acknowledge sex-specific risk factors, such as hypertension in pregnancy, and the benefit of treating hypertension in both men and women. In more recent years, hypertension awareness and treatment rates are higher in women than in men while blood pressure control rates are improving, but remain still lower in older hypertensive women. Differences have been described regarding the pattern of antihypertensive drug prescription and use in hypertensive men and women; women are more frequently treated with diuretics and less frequently with angiotensin-converting-enzyme (ACE)-inhibitors and angiotensin-receptors blockers. Calcium-antagonists appear to be particularly effective in women. Data from large clinical trials and meta-analyses offer strong evidence that the efficacy of the various drug classes in prevention of CV events does not differ by sex, and therefore the choice of the drug cannot be based only on this criterion in post- menopausal women. There are currently no specific blood pressure (BP) treatment goals for post-menopausal hypertension.

Background/aims: In patients with obesity, there is increased inflammation with attendant oxidative stress in perivascular adipose tissue. This has functional consequences with loss of vasodilator adipokine bioavailability. Part of the inflammatory response is mediated by increased activation of the renin-angiotensin-aldosterone axis. Therefore, this study was designed to investigate whether angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can improve the anticontractile function of perivascular adipose tissue., Methods: Segments of rat mesenteric small artery were dissected and mounted in a wire myograph and contracted to incremental doses of norepinephrine in the presence and absence of perivascular adipose tissue and in conditions of normal oxygenation or after hypoxia and incubated with captopril or telmisartan., Results: Vessels with perivascular adipose tissue contracted significantly less than arteries with perivascular adipose tissue removed under normal oxygenation conditions, indicating that perivascular adipose tissue exerts an anticontractile effect. Hypoxia induced a loss of this anticontractile effect which could be completely prevented with captopril or telmisartan., Conclusion: The in-vitro creation of a hypoxic environment can simulate the loss of anticontractile perivascular adipose tissue function seen in vivo in obese patients, and this can be prevented using inhibitors of the renin-angiotensin cascade.

Background: It has been previously demonstrated that dihydropyridine calcium channel blockers may possess antioxidant properties and might improve vascular structure. Combination treatment with an angiotensin-converting enzyme inhibitor may have additional advantages, compared with a thiazide diuretic, in this regard. The aim of the present study was, therefore, to investigate the effects of a short-term treatment with lercanidipine, and to compare two combination treatments: lercanidipine + enalapril vs. lercanidipine + hydrochlorothiazide on structural alterations in retinal arterioles, on skin capillary density and on large artery distensibility., Patients and Methods: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Then they were treated for 6 months with lercanidipine + enalapril (n=10) or lercanidipine + hydrochlorothiazide (n=10) combinations. Investigations were performed in basal condition, after appropriate washout of previous treatments, after 4 weeks of lercanidipine monotherapy treatment, and at the end of the combination treatment. Non-invasive measurements of wall-to-lumen ratio (W/L) and other morphological parameters of retinal arterioles using scanning laser Doppler flowmetry were performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). Capillary density was evaluated by capillaroscopy, whereas pulse wave velocity and central blood pressure were assessed by the Sphygmo-Cor device (AtCor Medical West Ryde, Australia)., Results: A significant improvement of W/L and of other indices of retinal artery structure was observed after treatment with lercanidipine alone, with a further improvement after treatment with lercanidipine + enalapril, whereas after treatment with lercanidipine + hydrochlorothiazide the improvement was no longer observed. A similar behaviour was observed for central SBP and DBP. Capillary density was increased only after treatment with lercanidipine + enalapril., Conclusion: Lercanidipine both in monotherapy and in combination with enalapril, was able to improve microvascular structure and to decrease central blood pressure, being thus a useful approach for both reducing blood pressure and improving vascular alterations in hypertension.

Background: Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach., Methods and Results: We investigated 40 individuals and patients, 24 of them were hypertensive patients and 16 normotensive individuals. All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and media-to-lumen ratio was measured. In addition, an evaluation of wall-to-lumen ratio of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles (r = 0.76, P < 0.001; P < 0.001, r(2) = 0.57)., Conclusion: A noninvasive and easily repeatable procedure (intraobserver and interobserver variation coefficient <13%) such as an evaluation of the arterioles in the fundus oculi by SLDF may provide similar information regarding microvascular morphology compared with an invasive, accurate and prognostically relevant micromyographic measurement of media-to-lumen ratio of subcutaneous small arteries.

Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media to lumen ratio, are frequently present in hypertensive and/or diabetic patients. However, the evaluation of microvascular structure is not an easy task. Among the methods that may be applied to humans, plethysmographic evaluation of small arteries and wire or pressure micromyography were extensively used in the last decades. Media to lumen ratio of small arteries evaluated by micromyography was demonstrated to possess a strong prognostic significance; however, its extensive evaluation is limited by the invasiveness of the assessment, since a biopsy of subcutaneous fat is needed. Non-invasive approaches were then proposed, including capillaroscopy, which provides information about microvascular rarefaction. Recently, the interest of investigators has focused on the retinal microvascular bed. In particular, a non-invasive measurement of wall thickness to internal lumen ratio of retinal arterioles using scanning laser Doppler flowmetry has been recently introduced. Preliminary data suggest a fairly good agreement between this approach and micromyographic measurements, generally considered the gold standard approach. Therefore, the evaluation of microvascular structure is progressively moving from bench to bedside, and it could represent, in the immediate future, an evaluation to be performed in all hypertensive patients, in order to obtain a better stratification of cardiovascular risk., (© 2011 Adis Data Information BV. All rights reserved.)

BACKGROUND. In hypertensive patients, endothelial dysfunction is associated with an increased incidence of cardiovascular events. Calcium-channel antagonists can reverse impaired endothelium-dependent vasodilation in different vascular districts, while conflicting results are found in the brachial artery. Aim. To investigate the effect of barnidipine in comparison with hydrochlorothiazide on endothelial function of hypertensives, as assessed by flow-mediated vasodilation (FMD) of the brachial artery. METHODS. Patients with mild to moderate hypertension (age range 26-67 years) were randomized to receive barnidipine or hydrochlorothiazide. A thorough clinical examination, including blood pressure (BP) measurement, was performed at randomization as well as after 6, 12 and 24 weeks. FMD and 24-h BP monitoring was performed at randomization, after 12 and 24 weeks. RESULTS. After 12 and 24 weeks of treatment, a significant reduction in clinic BP was observed in both groups. Furthermore, a significant reduction in 24-h SBP and DBP was observed in patients receiving barnidipine but not in those receiving diuretic. The percentage change in FMD was different between the two groups of patients treated with barnidipine (at 12 weeks +1.2 ± 2.2%, p = 0.023 and at 24 weeks +1.25 ± 3.15%, p = 0.16 from baseline) or with hydrochlorothiazide (at 12 weeks -1.0 ± 3.0. p = 0.09 and at 24 weeks -1.78 ± 2.9%, p = 0.015 from baseline). A significant difference in FMD changes between the two groups was confirmed by analysis of covariance (p = 0.031). CONCLUSIONS. In presence of a similar clinic BP reduction, an improvement of endothelial function was observed during treatment with barnidipine but not with hydrochlorothiazide, suggesting that the barnidipine may exert a favourable effect on endothelial dysfunction in hypertensive patients.

Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media:lumen ratio, are frequently present in hypertensive and/or diabetic patients and may represent the earliest alteration observed. In addition, media:lumen ratios of small arteries have a strong prognostic significance. However, no data are available about the structure of small resistance arteries of obese patients, particularly after weight loss. We have investigated 27 patients with severe obesity. Twelve of them were normotensive, and 15 were hypertensive. All of the obese patients underwent bariatric surgery. We compared results obtained with those observed in 13 normotensive lean controls and in 13 hypertensive lean patients. All of the subjects and patients underwent a biopsy of subcutaneous fat during surgical intervention. In 8 obese patients, a second biopsy was obtained after consistent weight loss, during a surgical intervention for abdominoplasty. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and structural parameters were measured. A concentration-response curve to acetylcholine was performed to evaluate endothelial function. Obese patients, independent from the presence of hypertension, show the presence of an increased media:lumen ratio and media cross-sectional area, together with an impaired endothelial-dependent vasodilatation. After surgical correction of obesity and consistent weight loss, a significant improvement of microvascular structure and of some oxidative stress/inflammation markers were observed. In conclusion, our data suggest that the presence of obesity is associated with structural alterations of subcutaneous small resistance arteries, mainly characterized by hypertrophic remodeling. Weight loss may improve microvascular structure.

It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.

Objective: Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome., Subjects: We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress., Results: Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels., Conclusion: Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

Context and Objective: It has been previously demonstrated that aldosterone may possess a strong profibrotic action in vitro and in animal models of genetic or experimental hypertension. Our aim was to evaluate whether such a profibrotic action is present also in the human microcirculation., Design and Patients: We investigated 13 patients with primary aldosteronism, seven patients with essential hypertension, and 10 normotensive controls. All subjects were submitted to a biopsy of gluteal sc fat tissue. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured., Main Outcome Measures: The total collagen content within the tunica media was detected (Sirius red staining and image analysis), and collagen subtypes were evaluated using polarized light microscopy; under this condition thicker type I collagen fibers appear orange or red, whereas thinner type III collagen fibers are yellow or green., Results: Tunica media to internal lumen ratio was significantly increased in primary aldosteronism and in essential hypertension compared with normotensive controls. Clinic blood pressure values were similar in primary aldosteronism and in essential hypertension, and greater than in normotensive controls. Normotensive controls had less total and type III collagen (3.23 +/- 0.58 and 1.60 +/- 0.22%, respectively) in respect to the two hypertensive groups (P < 0.001). Total collagen and type III vascular collagen were significantly greater in primary aldosteronism (total collagen, 8.17 +/- 1.38%; type III collagen, 6.06 +/- 0.74%; P < 0.05) than in essential hypertension (total collagen, 6.84 +/- 1.15%; type III collagen, 5.25 +/- 0.80%)., Conclusions: Our results indicate that, in small resistance arteries of patients with primary aldosteronism, a pronounced fibrosis may be detected, even more evident than in blood-pressure-matched patients with essential hypertension.