Search

Objective: Aortic stiffness and central pressure measurements have become increasingly important for the overall estimation of cardiovascular risk. The aim of this study is to verify whether the presence of stenosis in the carotid arteries due to atherosclerotic plaques may induce a bias in the measurement of carotid-femoral pulse wave velocity (PWV) and in the analysis of central pulse waveform variables assessed by carotid tonometry. Methods: Eighty-four patients (age: 67.1 ± 12.4 years) undergoing screening for carotid atherosclerosis were enrolled, divided into three groups according to carotid ultrasound findings (NASCET criteria): 28 patients without significant stenosis, 30 patients with bilateral plaques, and 26 patients with right or left monolateral stenosis. PWV and other variables derived from the central pulse waveform analysis (central blood pressure, augmentation index and forward and backward waves) were measured at both right and left carotid arteries by a validated PulsePen tonometer. A repeatability study was performed in 28 young healthy patients (age: 25.4 ± 2.9 years). Results: A high degree of correlation was found between bilateral measurements in all groups, and particularly in groups with monolateral carotid stenosis, with no significant difference attributable to lateralized stenosis. Right-left differences in asymmetric groups were 0.35 ± 5.12 mmHg (R2 = 0.960) for central blood pressure,-2.12 ± 7.39% (R2 = 0.743) for augmentation index, 0.64 ± 1.56 m/s (R2 = 0.947) for PWV, 0.08 ± 8.48 mmHg for forward wave (R2 = 0.742) and 0.35 ± 2.35 mmHg for backward wave (R2 = 0.907). Conclusion: Measurement of PWV and of variables derived from the central pulse waveform analysis by carotid tonometry is not biased by the presence of local atherosclerotic plaques.

Objective The index of maximal systolic acceleration ([AImax]: maximal systolic acceleration of the Doppler waveform divided by peak systolic velocity) shows diagnostic accuracy in screening of renal artery stenosis. This study aimed to determine whether an upstream factor of resistance, such as aortic valve stenosis (AVS), can affect Doppler parameters detected in the peripheral arteries. Methods In this prospective study, we measured the AImax in non-stenotic renal interlobar arteries of 62 patients with AVS. Patients were divided into three groups on the basis of severity of valvulopathy as follows: mild-to-moderate AVS (M-AVS; n = 24), intermediate AVS (I-AVS; n = 15), and severe AVS (S-AVS; n = 23) based on Nishimura’s criteria. Results The AImax in the renal parenchymal arteries was significantly lower in the S-AVS group (8.9 ± 3.6 s−1) than in the M-AVS (15.3 ± 3.8 s−1) and I-AVS groups (16.7 ± 5.2 s−1). The AImax was positively correlated with the aortic valve area and inversely correlated with the tranvalvular aortic pressure gradient. After aortic valve replacement, the AImax significantly increased from 10.7 ± 4.0 s−1 at baseline to 19.3 ± 4.4 s−1. Conclusions Proximal resistance can lead to diagnostic bias of Doppler parameters that are applied in the diagnosis of peripheral vasculopathies, particularly in renal artery stenosis.

Renal artery stenosis (RAS) has been shown to cause a reduction in the index of maximal systolic acceleration (AImax: the maximal acceleration of flow waveform in early systole divided by the peak systolic velocity) of blood in the renal interlobar arteries, caused by local dampening of the pulse wave. In previous studies, AImax demonstrated diagnostic accuracy in terms of negative predictive value, which is useful for screening, but had a relatively low specificity. We hypothesized that an upstream focal resistance, such as an aortic stenosis or aneurysm, could act in the same way as RAS, thus generating false positives in non-stenotic kidneys. We studied 226 patients who underwent a complete protocol for RAS screening. AImax was 6.2 ± 2.9 s–1 and 13.4 ± 3.5 s–1 (mean ± standard deviation) in stenotic and non-stenotic kidneys, respectively. Diagnostic accuracy of ultrasonography with respect to the benchmark of renal computed tomography or magnetic resonance angiography (significant RAS cutoff ≥50%) resulted in 97% sensitivity, 94% specificity and a negative and positive predictive value of 99% and 55%, respectively. Using logistic regression for unexpectedly low AImax in non-stenotic kidneys (AImax cutoff ≤ 9.0 s–1), aortic pathology, such as aortic valve stenosis or aortic arch dilation (as assessed by echocardiography), was found to be the only significant predictor (Χ2 = 33.8, p < 0.0001) of false positive cases compared with clinical and hemodynamic variables. We concluded that the aortic valvular and non-valvular pathology can act as a proximal resistance that can attenuate the Doppler flowmetric parameters, which explore the flow waveform in the renal parenchymal arterial circulation, thus mimicking the presence of a focal resistance in the peripheral vascular region explored.

Background Increased large arteries wall stiffness (AS) is a well known independent morbidity and mortality cardiovascular risk factor, not only related to hypertension and diabetets, but also induced by long standing systemic inflammation, as observed in inflammatory rheumatic or gut chronic diseases. Psoriatic arthritis (PsA) was also shown to increase cadiovascular morbidity, but this observation was commonly related with the associated occurrence of long term arthritis, disease activity and CV traditional risk factors Objectives To assess whether in a selected group of PsA patients, affected by recent onset (4–12 months) arthritis, not suffering from CV disease risk factors, evidence could be obtained of an early alteration of arterial wall function as expressed by an increased arterial pulse wave velocity (aPWV) and secondary reduced tonometric subendocardial viability ratio (tSEVR). Further, we evaluated if a 18 months (Mth) treatment with synthetic disease modifying antirheumatic drugs (sDMARD) other than cyclosporine, leading to a demonstrable target of clinical “minimal disease activity”(MDA) could modify such possible modifications Methods Conclusive data were obtained in a selected goup of 12 PsA patients (Pts) (CASPAR criteria classified) (M/F, 6/5; mean age, 50.8; range, 40–65) not suffering from axial spondylitis who firsly underwent (without any previous treatment) aPWV measurement (PulsePen, Diatecne Srl, Milan) and tSEVR calculation, and then were re-evaluated for the same calculations after a 18 Mth time of sDMARD treatment. Each of the PsA Pts had a 3–4 Mth follow up and showed to reach the target of stable MDA (with also ultrasound confirmed remission of active synovitis) after a 4–8 Mth treatment. Before treatment, the group of PsA Pts was compared with an age, body weight, CV parameters and risk factors–matched control group of voluntary 22 healthy subjects (M/F, 11/11; mean age, 51.3; range, 41–67) Results Before any treatment, aPWV was higher in the group of patients with PsA than in control subjects (median, 8.667 m/s vs 6.963 m/s, p Conclusions Early onset of PsA seems to be associated with already established and stable increase of AS. Subclinical previous phase of inflammation and length of psoriatic disease could be addressed as possible causes Disclosure of Interest None declared

Primary aldosteronism (PA), also known as Conn’s syndrome, is a frequent cause of secondary hypertension. If PA is due to a documented unilateral adrenal adenoma, adrenalectomy is the treatment of choice. Endocrine Society guidelines suggest monitoring potassium after adrenalectomy, while there is no mention of sodium disorders after surgery. Here we report the case of a patient with Conn’s syndrome who developed hyponatremia after surgery. This was an unexpected event in the course of the treatment, which sheds light on the fact that low levels of aldosterone strongly influence sodium concentration, and advises clinicians to monitor sodium after adrenalectomy.

ObjectiveAcromegaly is associated with increased cardiovascular morbidity and mortality and with specific heart and vascular abnormalities. The aim of our study was to investigate arterial stiffness using the ambulatory arterial stiffness index (AASI) and symmetric AASI (Sym-AASI), two indexes derived from 24-h ambulatory blood pressure monitoring (ABPM), in a group of normotensive and hypertensive patients with active acromegaly, compared with normotensive controls (NOR-CTR) or hypertensive controls (HYP-CTR).Subjects and methodsNinety-six consecutive patients with active acromegaly (46 males, mean age 49±14 years) underwent 24-h ABPM and evaluation of cardiovascular risk factors. Based on ABPM measurement, acromegalic patients were divided into 64 normotensive (normotensive acromegalic patients (NOR-ACRO)) and 32 hypertensive (hypertensive acromegalic patients (HYP-ACRO)) patients, and were compared with 35 normotensive (NOR-CTR) and 34 hypertensive (HYP-CTR) age-, sex,- and ABPM-matched control subjects.ResultsThe AASI and Sym-AASI indexes were significantly higher in acromegalic patients than in controls, either in the normotensive (NOR-ACRO vs NOR-CTR, PP=0.005 for Sym-AASI) or in the hypertensive (HYP-ACRO vs HYP-CTR, P=0.01 for AASI and P=0.01 for Sym-AASI) group. Multiple logistic regression analysis showed a significant association of the highest AASI tertile with serum IGF1 (P=0.034) in the whole acromegalic group.ConclusionAASIs are increased in acromegaly, independent of blood pressure (BP) elevation, and may have an important role in predicting cardiovascular risk in this disease.

Objective To gain insight into the regulation of cardiac apoptosis we studied the dose-response and time-course effects of angiotensin II (Ang II) infusion on ventricular cardiomyocyte apoptosis and on the expression of Bax and Bcl-2 genes and proteins. Study design and methods In the dose-response study, Ang II was infused subcutaneously at doses of 100, 200, 400, 800 and 1200 ng/kg per min for 14 days. In the time-course study, rats infused with Ang II at doses of 200 and 400 ng/kg per min were followed for 7 and 14 days. The cardiomyocyte apoptotic density was assessed by DNA end labelling (terminal deoxynucleotide nick-end labelling; TUNEL). Gene and protein expression of Bcl-2 and Bax were evaluated by reverse transcriptase-polymerase chain reaction and by Western blots. Results Systolic blood pressure and left ventricular mass were increased in a dose-dependent manner in Ang II-infused rats. A statistically significant increase in the rate of cardiac apoptosis and pro-apoptotic changes of Bcl-2 and Bax gene and protein expression was observed when high doses of Ang II (800-1200 ng/kg per min) were infused. A positive correlation of apoptotic density with Bax and a negative correlation with Bcl-2 and Bcl-2/Bax ratio were found. Cardiac apoptosis was greatly influenced by the timing of Ang II infusion. Losartan-treated Ang II-infused rats exhibited normalized systolic blood pressure, left ventricular weight, apoptosis, and Bax and Bcl-2 levels. Conclusions Our results are consistent with the pathophysiological role of Ang II in induction of cardiac apoptosis, and explain the cardioprotective effect of Ang II receptor antagonists.

Background Malignant hypertension is a condition characterized by severe hypertension and multi-organ ischemic complications. Albeit mortality and renal survival have improved with antihypertensive therapy, progression to end-stage renal disease remains a significant cause of morbidity and mortality. The underlying cause of malignant hypertension, which can be primary or secondary hypertension, is often difficult to identify and this can substantially affect the treatment outcomes, as we report here. Case presentation A 33-year-old woman presented with severe hypertension and acute renal failure. Initial evaluation demonstrated hyperreninemia with hyperaldosteronism and a possible renal artery stenosis at the contrast-enhanced CT scan. Although this data suggested the presence of a secondary form of hypertension, further exams excluded our first diagnosis of renal artery stenosis. Consequently, the patient did not undergo renal angiography (and the contrast media infusion associated with it), but she continued to be medically treated to achieve a tight blood pressure control. Our conservative approach was successful to induce renal function recovery over 2 years of follow-up. Conclusion This case highlights the difficulty in differentiating between primary and secondary forms of malignant hypertension, particularly when the patient presents with acute renal failure. Clinicians should consider renal artery ultrasound as a first level diagnostic technique, given that the presentation of primary malignant hypertension can often mimic a renal artery stenosis. Secondly, adequate control of blood pressure is essential for kidney function recovery, although this may require a long time.

The objective of the present study was to investigate the acute effects of alcohol on blood flow volume and velocity, on wall motion of superficial large arteries, and on systemic hemodynamics in humans. In 10 healthy volunteers small doses of alcohol were administered either orally (0.3 g/kg in 250 mL water) or intravenously (7.5 mg/kg/minute in 250 mL saline in 40 minutes). The effects of alcohol were compared with those of saline 250 mL infused for 40 minutes (6.25 mL/min). Blood velocity and systodiastolic changes of wall diameter were measured in the common carotid, femoral, and brachial arteries simultaneously with cardiac output and finger blood pressure. Skin temperature was measured at the cheek, hand, and toe. Ethanol administration caused a transitory blood pressure increase accompanied by a rise in peripheral resistances at 20 minutes. Arterial blood flow was not changed by either mode of alcohol administration at any of the measurement sites. However, this result was achieved through different compensatory mechanisms in each artery. In fact, mean carotid diameter increased after both oral and intravenous ethanol administration but remained unchanged at the brachial and femoral level. Mean blood velocity was reduced after alcohol administration at the carotid but was unchanged at the brachial and femoral level after oral or intravenous alcohol administration. Skin temperature increased 20 minutes after alcohol administration at all sites. This study shows that although acute alcohol administration does not change blood flow in superficial large arteries, it causes different autoregulatory local responses of vessel walls.

The aim of this study was to investigate the short‐term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone‐producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24‐hour, daytime, and nighttime BP; 24‐hour weighted SD of BP; and 24‐hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P

Baroreflex sensitivity (BRS) and central arterial function are significantly worsened after menopausal transition. This study tested the hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA) might contribute to prevent these adverse changes in the vascular function of ovariectomized rats, an animal model of experimental menopause.We randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL), sham surgery, normal diet; ovariectomized with normal diet (OVX) and ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d) (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic response to phenylephrine-induced blood pressure increase, while large artery function was estimated by the graphical analysis of the aortic pressure wave (diastolic to systolic pressure-time integral ratio, DTI/STI).Ovariectomy caused a significant decrease in BRS (CTRL: 6.23±0.68ms/mmHg; OVX: 2.85±0.75; p0.001). n-3 PUFA supplementation prevented part of the decline of BRS caused by surgical menopause (OVX+O3: 4.75±0.53; p0.01 vs OVX). In animals treated with n-3 PUFA, the central arterial pressure profile did not show the changes in DTI/STI ratio seen in OVX (OVX: 3.31±1.72; OVX+O3: 3.83±1.52; p0.01).In an experimental model of menopause, treatment with n-3 PUFA normalized central hemodynamics and prevented the decrease in BRS, associated with the reduction of compliance of the arterial wall. These findings suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of postmenopausal vascular disease.

Our objective was to determine if urinary bladder distention modifies the sensitivity of the baroreceptor-heart rate reflex in hypertensive and control subjects. The baroreceptor-heart rate reflex sensitivity was measured in 15 male patients (mean age 37+/-8 years) with mild untreated hypertension (mean 163+/-8/ 95+/-12 mmHg) and 17 age- and sex-matched control subjects before and after urinary bladder distention. Bladder filling was performed infusing saline heated to 37 degrees C via a urinary catheter; the volume infused in each patient corresponded to that which caused the urge to void without reaching the pain threshold. The baroreceptor-heart rate reflex sensitivity was determined correlating the variations of the systolic pressure and of the peak blood flow velocity in the common carotid artery with the variations of the ECG RR' interval of the following heart beat, both during spontaneous and phenylephrine-induced fluctuations of the haemodynamic variables. After bladder distention the diastolic pressure of the hypertensive subjects increased significantly (95+/-12 vs. 100+/-12 mmHg: P < 0.02), whereas the heart rate decreased (RR= 873+/-70 vs. 926+/-80 ms; P < 0.005). These parameters were unchanged in the normotensive subjects (84+/-9 vs. 83+/-8 mmHg and 914+/-158 vs. 913+/-140 ms, respectively). The baroreceptor-heart rate reflex sensitivity, measured on the basis of spontaneous pressure and carotid blood flow velocity fluctuations in relationship to RR changes, decreased in the normotensive subjects after bladder distention (10.7+/-4.6 vs. 9.4+/-2.7 ms/mmHg; P < 0.05 and 423+/-99 vs. 356+/-102 ms/kHz; P < 0.01, respectively), whereas it increased in the hypertensive patients (6.9 +/- 3.6 vs. 8.3 +/- 2.8 ms/mmHg; P < 0.03, and 332 +/- 86 vs. 381+/-97 ms/kHz; P < 0.03 respectively). After bladder distention and phenylephrine administration the baroreceptor-heart rate reflex sensitivity, measured by the correlation between systolic pressure and RR interval, increased only in the hypertensive group (10.2+/-5.4 vs. 15.2+/-7.7 ms/mmHg; P < 0.005). In conclusion urinary bladder distention provokes in hypertensives but not normotensive controls a brisk parasympathetic response of the component of the baroreceptor-heart rate reflex which controls heart rate.

Background: Menopause is associated with increased arterial stiffness, an independent marker of cardiovascular risk. Omega-3 polyunsaturated fatty acids (N3-PUFAs) are thought to have multiple cardiovascular benefits, including prevention of arterial stiffness. We investigated whether treatment with N3-PUFA prevents increase in arterial stiffness in ovariectomized rats, an animal model of experimental menopause. Methods: A total of 43 Wistar rats, 2 months old, were divided into 3 groups, control, sham surgery, normal diet (CTRL, n = 15); ovariectomy, normal diet (OVX, n = 14); and ovariectomy with N3-PUFA supplementation (0.8 g/kg/d in daily gavages administration; OVX + O3, n = 14). Two months after surgery, carotid–femoral pulse wave velocity (PWV) and arterial blood pressure (BP) were measured by carotid and femoral cannulation. Aortic morphometric measurements were performed after dissection. Results: Ovariectomy caused a significant increase in BP ( P < .05), PWV ( P < .0001), and elastic modulus ( P = .001) compared to CTRL. After ovariectomy, N3-PUFA supplementation completely prevented increase in arterial stiffness ( P < .0001 vs OVX) and BP ( P < .05 vs OVX) and resulted in a significant increase in body weight and aortic thickness. Conclusions: In an experimental model of menopause, N3-PUFA supplementation prevents arterial stiffening and other vascular changes induced by ovariectomy. These results represent a therapeutic benefit of N3-PUFAs in prevention of postmenopausal cardiovascular disease.

Abstract Left ventricular hypertrophy with diffuse intermyocardiocytic fibrosis is a feature of uremia. The role of blood pressure and/or other cardiovascular uremic risk factors in cardiac remodeling is still uncertain. To determine the extent to which improvement of kidney function and the control of uremia-related risk factors are associated with a reduction of myocardial injury, we evaluated the effect of dietary protein restriction or the angiotensin-converting enzyme inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after subtotal nephrectomy, Wistar rats were allocated to receive drinking water solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet (6%) (group 3) for 12 weeks. Groups 2 and 3 showed a comparable efficacy in preventing the expected rise in creatininemia, urinary protein excretion, and glomerulosclerosis. However, hypertension development was prevented only in group 2. Groups 1 and 3 developed a significant ( P P

Renal artery stenosis is frequently considered in the diagnosis of severe hypertension and renal insufficiency, but the benefits of screening and the choice of imaging modalities is controversial. Sonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA), and conventional angiography are all used and each has advantages and disadvantages. However, performance and interpretation of each requires significant experience and expertise. Since there are no clear data or consensus on the choice of imaging modalities, this should be based on the level of expertise that is available.

The mechanisms underlying the increased cardiovascular risk after menopause are poorly understood. Estrogens modulate the cardiac renin-angiotensin system (RAS) and influence cardiac adaptation to afterload. To investigate whether the loss of the natural inhibition of the RAS by estrogen may be linked to an increase of cardiac apoptosis, we studied 17β-estradiol (E2) and/or angiotensin-converting enzyme (ACE) inhibitor treatment effects on cardiomyocyte survival in ovariectomized spontaneously hypertensive rats (SHRs).Five groups of female SHRs were evaluated for 8 weeks. One group served as nonovariectomized control; the other four groups underwent bilateral ovariectomy and were randomized to receive 60-day-release pellets containing placebo or 0.5 mg of E2, the ACE inhibitor ramipril at the dosage of 2.5 mg/kg per day, or the combination of the two treatments.Ovariectomy increased cardiomyocyte apoptosis and induced proapoptotic changes of Bcl-2 and Bax genes and proteins. These modifications were associated with an upregulation of ACE and angiotensin II type 1 (AT1) receptor genes. Ramipril was as effective as E2 in preventing cardiac apoptosis and in restoring cardiac brain natriuretic peptide in association with reduced cardiac ACE and AT1 receptor gene expression. In contrast to the ramipril treatment, the favorable effect of E2 on cardiac apoptosis occurred independently from changes in SBP. No synergistic effect was observed when the two treatments were combined.These data show that ovariectomy stimulates myocardium apoptosis by a mechanism involving Bax and Bcl-2 genes. The antiapoptotic effect of E2 and ACE inhibitor treatment was linked to a downregulation of cardiac RAS.

The concept of vulnerable atherosclerotic plaque in defining the prognostic risk for plaque rupture and thromboembolic complications is an attempt to go beyond the concept of the risk as only related to the degree of the consequent stenosis. However, interventional trials still depend on the evaluation of the degree of stenosis, used as endpoint and do not use plaque characteristics such as aspect, morphology, structure, and mechanics. Unfortunately, no consensus has yet been reached about how to define objective criteria and methodologies for assessing plaque characteristics.

BACKGROUND: The aim of the present study was to compare glomerular permeability alterations associated with experimental hypertension models known to have different effects on the circulating renin-angiotensin system (RAS). METHODS: Five groups, 10 animals each, were studied. One group served as a nonhypertensive control. The other four groups of hypertensive animals were composed of spontaneously hypertensive rats, deoxycorticosterone acetate hypertensive rats, Goldblatt two-kidney, one-clip rats, and a group of Wistar rats infused with angiotensin II (200 ng/kg/min). Tail-cuff sphygmomanometric systolic blood pressure (BP), albumin permeability determined in isolated glomeruli exposed to oncotic gradients (P(alb)), glomerular filtration rate (GFR, iopamidol method), plasma renin activity (PRA), and albuminuria were evaluated. RESULTS: Alterations in P(alb) and albumin excretion rate were more evident in the experimental models with an activation of the RAS despite similar levels of systolic BP and GFR. A positive correlation was found between P(alb) and albuminuria (r = 0.51; P < .001) and between systolic BP and albuminuria (r = 0.37; P < .01). No relation was found between systolic BP and P(alb). CONCLUSIONS: The present study indicates that the activation of the RAS plays a significant role in the development of glomerular albumin permeability defects in hypertensive models and may contribute to the mechanisms that lead to target organ damage in hypertension.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (Palb) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg · kg−1 · day−1. Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of Palb in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced Palb significantly in concentration ranges from 10−6 to 10−14 mol/l compared with results in control glomeruli. The effect on Palb may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the Palb defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

The aim of the present study was to determine whether changes of carotid wall shear stress induced by changes in blood viscosity after diuretic administration cause carotid arterial dilatation in elderly hypertensives, as reported in the cat. Arterial wall shear rate (ultrasound technique, profilmeter FRP III), the systo-diastolic diameter (echotracking technique) and the mean blood flow velocity and volume of the common carotid artery, the blood viscosity (rotational viscometer) and the finger arterial blood pressure (Finapress Ohmeda) were measured in 12 young volunteers (aged 25+/-2 years) and in 12 elderly hypertensives (aged 80+/-4 years) treated with short-acting calcium antagonists up to 24h before the study, both at baseline and after intravenous furosemide infusion (0.5mg/min), when the haematocrit had increased by at least two percentage points. After furosemide administration the mean arterial blood pressure decreased and blood viscosity and carotid systolic shear stress increased in both groups. However, common carotid artery diameter increased only in the young controls but not in the elderly hypertensives. These data show that an increase in carotid shear stress caused by haemoconcentration induces carotid vasodilatation only in young healthy subjects, and not in elderly hypertensives. This effect may be related to impaired endothelium function and/or arterial wall mechanics.

The effects of ethanol administered orally (300 mg/kg in 250 ml of water) or intravenously (7.5 mg·min-1·kg-1 in 250 ml of saline over 40 min) on common carotid haemodynamics, wall mechanics and baroreflex sensitivity were compared with the effects of the intravenous infusion of 250 ml of saline. Ethanol or saline was administered to 10 healthy volunteers after 30 min of supine rest, and measurements were obtained 40 min (median; range 34–46 min) after administration. After ethanol administration, the plasma alcohol level rose from 0 to 0.3±0.07 g/l. Mean arterial blood pressure had risen slightly at 20 min, but was normalized by 40 min, the time at which the haemodynamic study was performed. Heart rate decreased after infusion of either saline or alcohol, but was unchanged after oral ethanol administration. Both oral and intravenous ethanol administration were associated with significant decreases in baroreflex sensitivity, carotid shear stress and blood velocity, compared with resting values, while the mean carotid artery diameter was increased, and blood viscosity and mean blood flow were unchanged. No changes were observed in these parameters after saline administration. Ethanol, administered either intravenously or orally, increased the stiffness of the carotid artery and decreased the pulsatility (systo–diastolic changes) of its diameter. A direct, statistically significant correlation was found between the decrease in shear stress and the decrease in baroreflex heart rate control sensitivity after both modes of alcohol administration, while no such correlation was found between the increase in the Peterson elastic modulus and the decrease in carotid diameter pulsatility on the one hand or the decrease in baroreflex sensitivity on the other. In conclusion, reduced shear stress associated with vasodilatation of the carotid artery wall may contribute to the decrease in baroreflex sensitivity observed after acute ethanol administration.

Objective To study the effects of aortography and of aortic counterflow bolus injection per se on regional and systemic haemodynamics in hypertensives in comparison to normotensive matched controls. Design and methods Mean blood velocity (MBV) and pulsatility index (PI) - as an index of regional vascular resistance - by the Doppler technique, at the femoral, common carotid and brachial arteries, finger arterial pressure and electrocardiographic R-R' interval were monitored beat-by-beat, before, during and for 3 min following counterflow bolus injections into the abdominal aorta of 40 ml/2.6 s of iopamidol (I), iso-osmolar mannitol (M) and 0.9 N saline (S), in 11 hypertensive and nine normotensive patients. Results After bolus injection of iopamidol, MBV increased to a peak at 35 ± 5 s, both in normotensive (ΔMBV versus baseline +16.7 ± 9.9 cm/s; P

Blood flow induces shear forces acting on the vessel wall1-2. These forces influence endothelium structure and metabolism3-6 and the mechanical behaviour of the arterial wall.2 The arterial wall shear stress7 is representative of these shear forces; it is the product of blood viscosity and the velocity gradient near the endothelium (shear rate).

The shear stress of blood in arteries is an important parameter for the diagnosis of hypertension risks, even if its ultimate implications are not yet fully understood. The evaluation of this parameter requires the contemporaneous measurements of viscosity and shear rate, the latter being the gradient of the blood velocity near the vessel wall; remark that the shear stress should be measured during at least one complete heart beat, in order to provide useful diagnostic information.

To gauge the influence of renovascular resistance changes on blood flow velocity pulsatility in kidneys of hypertensive patients by means of the ultrasonic colour and pulsed-wave Doppler method, since we have previously shown in normotensive subjects that the blood flow velocity pulsatility in renal interlobar arteries varies with changes in renovascular resistance.In six male patients with primary hypertension, renal blood flow velocity profiles were investigated by means of duplex ultrasound. Single-kidney renovascular resistance was assessed by measurements of split renal function (gamma-camera renography), renal plasma flow (steady-state para-aminohippurate clearance) and cuff blood pressure. The pulsatility index of the blood flow velocity spectrum in the renal interlobar artery and renovascular resistance were measured either at rest, during infusion of angiotensin II, or after angiotensin converting enzyme inhibition.A significant correlation existed between pulsatility index and renovascular resistance (r = 0.50, P0.002), which did not improve after correction for the blood pressure pulsatility. Changes of pulsatility index were more closely related (r = 0.64, P0.001) to the corresponding changes in renovascular resistance.With the two-dimensional image-guided colour and pulsed-wave Doppler method it is possible to assess semiquantitatively small intra-individual changes in renovascular resistance in hypertensive patients by means of pulsatility index measurements. Pharmacologically induced alterations in renovascular haemodynamics may therefore be evaluated with this technique.

This study was designed to better characterise in humans the mechanism of action of rilmenidine, a new antihypertensive oxazoline derivative. The functional relationship between hypotensive response, adrenergic nerve activity and platelet α2-adrenoceptor number and function was evaluated in hypertensive subjects, both before and after prolonged treatment with this drug. The effect of rilmenidine were compared with those induced by a diuretic drug (hydrochlorothiazide). After 1 month of placebo, 24 patients with essential hypertension were randomly allocated to either rilmenidine 1 mg once daily or hydrochlorothiazide 25 mg once daily. At the end of the first month of treatment, the 2 drugs were combined in the patients whose diastolic blood pressure was higher than 90 mmHg. On days, 0, 30, and 60, the number and affinity of blood platelet α2-adrenoceptors were measured by 3H-yohimbine labelling, and plasma catecholamines were determined. On days 0 and 30, platelet aggregation was also ossessed. The results show that the administration of rilmenidine exerts significant and lasting antihypertensive activity. This effect, however, is not associated with a modification in platelet α2-adrenoceptor density and function, nor does it seem to affect catecholamine plasma levels, thus suggesting a negligible role for α2-adrenoceptor stimulation in the antihypertensive action of rilmenidine.

The pulsatility index (PI) of blood flow velocities has been reported to vary with changes in peripheral vascular resistance. Since blood flow velocities can easily be detected with the Echo-Color-Doppler technique in interlobar arteries of normally positioned kidneys, we tried in six healthy volunteers to estimate pharmacological induced variations in renal plasma flow (RPF) and renovascular resistance (RVR) by means of PI measurements. In this study no significant correlation between the absolute values of PI and RVR was found. In order to correct PI for different blood pressure-inputs to the renal artery, PI was divided by the pulsatility of the systemic arterial pressure, i.e. the 'blood pressure index' [BPI = (SAD-DAP)/MAP)], resulting in the 'velocity blood-pressure index' (VBI = PI/BPI), which was significantly correlated with RVR (r = 0.54, P less than 0.01). The pharmacological induced changes of RPF and RVR (delta RPF, delta RVR) were also correlated to the respective changes of PI and VBI (delta PI, delta VBI), with the highest significance when delta VBI was plotted against delta RVR (r = 0.83, P less than 0.0001). VBI, i.e. the pulsatility index of blood flow velocities as corrected for the pulsatility of the driving force, may be a tool for noninvasive assessment of changes in RVR and thereby of importance for the diagnosis and follow-up of renovascular diseases.

Hypotension is a common problem in patients on hemodialysis. To further investigate this problem, the number of platelet alpha 2-adrenoceptors and the activity of lymphomonocyte beta 2-adrenoceptors were measured in 10 hemodialyzed patients with normal blood pressure and in 10 sex- and age-matched persistently hypotensive hemodialyzed patients. Density of alpha 2-adrenoceptors was assessed by the specific binding of 3H-yohimbine to intact platelets, while the function of beta 2-adrenoceptors was estimated by the production of cAMP after the exposure of lymphomonocytes to isoprenaline. The maximal number of alpha 2-adrenoceptors was increased in the hypotensive compared to the normotensive group (262.13 vs. 77.21 fmol/mg protein; p < 0.01). Plasma norepinephrine was higher in the hypotensive than in the normotensive uremic patients (640 +/- 195 vs. 344 +/- 156 pg/ml; p < 0.01). Plasma epinephrine did not differ in the two groups (90 +/- 30 vs. 94 +/- 24 pg/ml). The amount of cAMP, produced by stimulation of lymphomonocytes, was lower in the hypotensive than that in the normotensive uremic patients (7.7 +/- 2.4 vs. 15.6 +/- 5.4 pmol/10(6) cells; p < 0.002). The increased number of alpha 2-adrenoceptors together with a high level of norepinephrine and reduced activity of adenylate cyclase (coupled with beta 2-adrenoceptors) support the hypothesis that hypotension in the hemodialyzed uremic patients may be related to a defect in adrenoceptor coupling mechanisms.

Blood flow in superficial vessels was measured by means of combined two-dimensional and continuous-wave Doppler echography. In vitro validation of the technique showed precision to within 10\% at flow rates greater than 300 ml/min. Assessment of common carotid artery blood flow was used to calculate vascular resistance in a single-blind, crossover study of 16 elderly patients over the age of 60 years (mean 67.7 +/- 6.5) with essential hypertension. The pulsatility index of the brachial artery was also determined. Before the study patients had previously received either placebo (twice a day) for 2 weeks or slow-release (SR) nicardipine (40 mg twice a day) for 2 months. During the study patients received a single 40 mg dose of nicardipine SR, after which mean arterial blood pressure decreased from 131 +/- 11 to 110 +/- 10 mm Hg (p less than 0.001) and from 122 +/- 13 to 108 +/- 11 mm Hg (p less than 0.001) in patients who had previously received placebo and nicardipine, respectively. Carotid vascular resistance decreased from 14.6 +/- 2.9 to 10.4 +/- 2.8 mm Hg.sec.ml-1 (p less than 0.001) and from 14.6 +/- 4.1 to 11.0 +/- 2.0 mm Hg.sec.ml-1 (p less than 0.01), respectively. The pulsatility index of the brachial artery changed from 9.4 +/- 4.4 to 9.7 +/- 8.3 and from 8.2 +/- 4.3 to 9.4 +/- 4.1, respectively (not significant). These data show that nicardipine SR reduces resistance both in the common carotid artery and in the brachial artery. Furthermore this drug appears to have an additional effect on the distensibility of the large arteries.

Hypertension in the obese may be related to hyperinsulinaemia. To investigate this relationship further, we infused somatostatin (250 micrograms/h in 100 ml saline) or saline, single-blind and in a random order, for 10 h in seven obese hyperinsulinaemic hypertensive patients and in seven normo-insulinaemic hypertensive controls. Every 2 h, blood pressure, plasma insulin, glucose, sodium, potassium, renin, cortisol and aldosterone concentrations and the urinary sodium:creatinine ratio were determined. Two hours after the somatostatin infusion was started, mean arterial blood pressure was significantly reduced in the obese hyperinsulinaemic patients (from 128 +/- 11 to 114 +/- 11 mmHg, P less than 0.05) but not in the controls and this reduction persisted throughout the study. The somatostatin infusion reduced plasma insulin and increased plasma glucose similarly in both groups. Plasma sodium, potassium, renin, cortisol and aldosterone concentrations and the urinary sodium:creatinine ratio were unchanged after the somatostatin infusion. These results suggest that hyperinsulinaemia could help sustain the blood pressure rise in obesity.

In a previous study we have shown that chronic treatment with indapamide increases baroreceptor sensitivity and reduces vascular reactivity, to pressor doses of noradrenaline (1). These observations suggest an action of the drug on blood vessels. To further investigate this point, we performed this study with the aim of establish whether the changes in baroreceptor sensitivity induced by chronic treatment with indapamide could be related to changes in vascular peripheral resistances.

The brachial arterial compliance and the carotid blood flow were determined in 16 hypertensives older than 60 years (60–85; 67 ± 6.5), after 15 days of placebo or 2 months of therapy with nicardipine SR (40 mg b.i.d.), administered randomly following a crossover design, in a single-blind protocol. The hemodynamic parameters were determined 8 h after the last pill of nicardipine SR was taken. The study was performed both before and 2 h after the administration of 40 mg of nicardipine. Mean arterial blood pressure was significantly reduced after 40 mg of nicardipine, both in the patients on placebo (130 ± 12 vs 112 ± 13 mmHg; P < 0.001) and in the patients receiving chronic treatment with nicardipine SR (118 ± 13 vs 108 ± 10 mmHg; P < 0.01).

To assess the acute effects of alcohol on baroreceptor reflex in moderate and heavy drinkers with essential hypertension and in healthy subjects who drank moderately, four groups of age and sex matched subjects were studied. Group 1 consisted of 10 healthy subjects (age range 21-50 (mean 37.4(10.5) years), who usually drank less than 200 g of alcohol per week; group 2 patients (age range 21-50 (mean 37.4(10.3) years) with mild or moderate essential hypertension and whose weekly alcohol consumption was less than 200 g; and groups 3 and 4 patients with mild or moderate hypertension (age range 21-50 (mean 37.2(10.2) years and 21-52 (mean 38.1(10.4) years respectively), who usually drank greater than 700 g of alcohol per week. In groups 1-3 an infusion of alcohol (7 mg.kg-1.min-1) in 500 ml of 5\% glucose was administered for 1 h to keep blood concentrations constant (6-7 g.litre-1), whereas in group 4 the dose was doubled (blood concentration 10-11 g.litre-1). Baroreceptor sensitivity was measured by the phenylephrine method before and after alcohol infusion and one or two days later before and after infusion of 500 ml of 5\% glucose. In healthy subjects and in moderate drinkers with hypertension the alcohol reduced baroreflex sensitivity significantly (from 17.5(9.5) to 13.8(8.4); p less than 0.01 and from 15(10) to 10.5(6.7) ms.mmHg-1, p less than 0.01 respectively), whereas in the heavy drinkers with hypertension it was significantly reduced only at the highest dose of alcohol (from 12.5(6) to 7.9(3.5) ms.mmHg-1; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of long-term treatment with indapamide in platelet alpha 2-adrenoceptors has been evaluated in 10 patients with essential hypertension, in a double-blind, cross-over study with placebo. After three months of therapy, indapamide significantly reduced mean blood pressure (from 137 +/- 12 to 116 +/- 6 mm Hg, p less than 0.001), whereas heart rate did not change (from 72 +/- 8 to 73 +/- 7 beats/minute). At the same time, platelet alpha 2-adrenoceptor number increased (from 168.2 +/- 48.4 to 256.8 +/- 14.5 fmol/mg protein, p less than 0.02), whereas the dissociation constant did not change (from 3.79 +/- 2.9 to 4.97 +/- 4.48). The plasma norepinephrine level was significantly reduced after long-term treatment with indapamide (from 275 +/- 118 to 210 +/- 56 pg/ml, p less than 0.02). These results bring about an inhibition of norepinephrine release from sympathetic nerve endings with a likely secondary increase of the number of platelet alpha 2-adrenoceptors.