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M Volpe

Publications and source records attributed to M Volpe.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats.

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.

Animals↗
PubMed1997

Intrarenal determinants of sodium retention in mild heart failure: effects of angiotensin-converting enzyme inhibition.

The onset and the mechanisms leading to Na+ retention in incipient congestive heart failure (CHF) have not been systematically investigated. To investigate renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (HF) off treatment (left ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake (250 mmol/d). Six patients were studied again after 6 weeks of treatment with enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular filtration rate were similarly increased in both normal subjects and mild HF patients. In spite of comparable increases of filtered Na+ in the two groups, fractional excretion of Na+, fractional clearance of free water, and fractional excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects and were reduced in patients with mild HF. During enalapril treatment, in the mild HF patients the cumulative Na+ balance was restored to normal; furthermore, enalapril significantly attenuated the abnormalities in the distal delivery of Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the proximal nephron is associated with Na+ retention in response to increased salt intake in the early or mild stages of HF. These abnormalities of renal Na+ handling are largely reversed by enalapril.

Adult↗
PubMed1997

Opposite feedback control of renin and aldosterone biosynthesis in the adrenal cortex by angiotensin II AT1-subtype receptors.

The aims of this study were to identify whether tissue renin is regulated by a negative-feedback mechanism produced by locally generated angiotensin (Ang II) in the adrenal cortex and to detect the pathway of Ang II modulation. For this purpose, in 36 12-week old, salt-restricted, nephrectomized Sprague-Dawley rats, we studied the effects of the Ang II AT1-subtype receptor antagonist losartan and of the Ang II AT2-subtype receptor antagonist PD123319 on renin mRNA and activity, aldosterone synthase mRNA, and AT1a-, AT1b-, and AT2-subtype receptor expression in the adrenal cortex. Ten additional rats, kept on a regular diet and then nephrectomized, were also studied. In salt-restricted, nephrectomized rats, losartan administration caused increases of adrenal renin mRNA (P<.05) and activity (P<.05) and a concomitant reduction of aldosterone synthase mRNA (P<.05). In addition, after losartan AT1b, receptor mRNA was reduced (P<.05), AT1a receptor mRNA was unchanged, and AT2 mRNA was increased (P<.05). PD123319 did not significantly modify any of these parameters. In conclusion, in salt-restricted, nephrectomized rats, selective antagonism of AT1-subtype receptors stimulates the expression and the activity of renin in the adrenal cortex. This observation demonstrates that Ang II locally formed in the adrenal cortex exerts a modulatory negative-feedback action on adrenal renin biosynthesis independent of the influence of the circulating renin-Ang system; this action is largely mediated through the AT1b-subtype receptors.

Adrenal Cortex↗
PubMed1997

Role of tissue renin in the regulation of aldosterone biosynthesis in the adrenal cortex of nephrectomized rats.

The aim of the study was to investigate whether the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in the adrenal gland and to explore the mechanisms of this action. Twelve-week-old male Sprague-Dawley rats were studied: 22 rats were maintained on a regular diet; 27 and 22 rats received a low salt diet with and without treatment, respectively, with the angiotensin II (Ang II) AT1-subtype receptor antagonist losartan (10 mg/kg per day). A fraction of each group of rats underwent bilateral nephrectomy (n = 12, 15, and 10, respectively) and was killed 48 hours later. In an additional group of 24 (12 intact and 12 nephrectomized) rats, the effects of the Ang II AT2-subtype receptor antagonist PD123319 were investigated. In intact rats, plasma renin activity (PRA) and adrenal renin activity and expression were progressively raised by salt restriction and losartan, whereas aldosterone synthase mRNA and plasma aldosterone (PA) levels were increased by salt restriction and reduced by losartan. Forty-eight hours after nephrectomy, PRA fell to undetectable levels; in contrast, adrenal renin expression, assessed by semiquantitative reverse-transcriptase polymerase chain reaction (using GAPDH as a standard for gene expression), showed an 18-fold increase and was further increased after salt restriction and losartan (all P < .05). Also, adrenal renin activity was raised after nephrectomy and further increased after salt restriction (P < .05) and losartan. Cytochrome P450 aldosterone synthase expression in the adrenal cortex was stimulated by nephrectomy alone and by nephrectomy combined with low salt intake (P < .05), with consequent increases in PA concentrations. In losartan-treated salt-restricted nephrectomized rats, cytochrome P450 aldosterone synthase expression (P < .05 versus nephrectomy alone and nephrectomy plus salt restriction) and PA concentrations were diminished (P < .05) in spite of the observed increases of adrenal renin expression. The AT2-receptor antagonism did not significantly affect PRA, adrenal renin, and aldosterone biosynthesis and production in either intact or nephrectomized salt-restricted rats. These results demonstrate that the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in vivo. This action is mediated primarily via the Ang II AT1-subtype receptors.

Adrenal Glands↗
PubMed1996

Association and cosegregation of stroke with impaired endothelium-dependent vasorelaxation in stroke prone, spontaneously hypertensive rats.

While hypertension is a major risk factor for stroke, it is not its sole determinant. Despite similar blood pressures, spontaneously hypertensive rats (SHR) do not share the predisposition to cerebrovascular disease typical of stroke-prone spontaneously hypertensive rats (SHRSP). We investigated vascular function in male SHR and SHRSP as well as in SHRSP/SHR-F2 hybrid animals. Animals were maintained on the appropriate dietary regimen necessary for the manifestation of stroke. Among the hybrid animals, a group of stroke-prone and a group of stroke-resistant rats were selected. Blood pressure was similar in all groups. Endothelium-independent vascular reactivity tested on isolated rings of thoracic aorta and basilar artery after death showed similar contractile and dilatory responses to serotonin and nitroglycerin, respectively, in all groups. In contrast, endothelium-dependent relaxation, in response to acetylcholine or substance P, was markedly reduced in SHRSP compared with SHR. Similarly, reduced vasodilatory responses were present in aortae of F2 rats that had suffered a stroke when compared with SHR or F2 rats resistant to stroke. The observed association and cosegregation of stroke with significant and specific impairment of endothelium-dependent vasorelaxation among SHRSP and stroke-prone F2 hybrids, respectively, suggest a potential causal role of altered endothelium-dependent vascular relaxation in the pathogenesis of stroke.

Acetylcholine↗
PubMed1996

Influence of digitalis on left ventricular functional response to exercise in congestive heart failure.

This was a double-blind, placebo-controlled, crossover study designed to determine the influence of digitalis treatment on left ventricular (LV) response to physical exercise in patients with congestive heart failure (CHF). In 10 patients with CHF (ejection fraction 29 +/- 2%), LV function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed during control conditions and after a 3-week treatment with digoxin (0.25 mg/day orally) or placebo. Ten normal volunteers matched for sex and age constituted the control group. In normals, exercise ejection fraction and end-diastolic volume increased (both p <0.001), while end-systolic volume decreased progressively (p <0.001). In control conditions, patients with CHF had a sharp increase in heart rate during exercise, while ejection fraction did not change; both end-diastolic and end-systolic volumes increased significantly (both p <0.001) during exercise. During digoxin treatment, heart rate response to exercise recorded in patients with CHF was comparable to that recorded in normal subjects. In addition, a significant increase in ejection fraction during exercise was detected (P <0.001), and the increase in end-systolic volume was significantly smaller than that observed in control conditions (p <0.05). When patients received placebo, the responses of LV function to exercise were comparable to those observed in control conditions. These findings demonstrate that digitalis has a favorable influence on LV functional adaptation to exercise in CHF.

Adult↗
PubMed1996

Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease.

Stroke is a complex disorder with a poorly understood multifactorial and polygenic aetiology. We used the stroke-prone spontaneously hypertensive rat (SHRSP) as a model organism, mated it with the stroke-resistant spontaneously hypertensive rat (SHR) and performed a genome-wide screen in the resultant F2 cohort where latency until stroke, but not hypertension (a major confounder) segregated. We identified three major quantitative trait loci, STR1-3, with lod scores of 7.4, 4.7 and 3.0, respectively, that account for 28% of the overall phenotypic variance. STR2 colocalizes with the genes encoding atrial and brain natriuretic factor, peptides with important vasoactive properties. Our results demonstrate the existence of primary, blood pressure-independent genetic factors predisposing to a complex form of stroke.

Animals↗
PubMed1996

Midwall LV mechanics in rats with or without renovascular hypertension: effect of different Na+ intakes.

Supranormal left ventricular (LV) function has been reported in one-kidney, one-clip (1K,1C) and two-kidney, one-clip (2K,1C) Goldblatt hypertension. However, this finding might be at least partially due to mismatching endocardial rather than midwall fractional shortening to mean end-systolic stress. Accordingly, relations of echocardiographic endocardial and midwall shortening to circumferential end-systolic stress were calculated in 40 Wistar rats on 0.4% NaCl (r = -0.92, SE of estimate = 4.3% and r = -0.62, SE of estimate = 3.2%, both P < 0.0001). Midwall shortening as a percentage of predicted was related to LV chamber diameter in normal animals (r = 0.56, P < 0.0001). Endocardial and midwall shortening were compared as percentage of the normal values predicted from wall stress in 34 2K,1C and 19 1K,1C on 0.4% Na+ 8-9 wk after surgery. Use of midwall shortening reduced the number of these hypertensive rats with supranormal observed-to-predicted shortening ratio from 28 to 7.5% (P < 0.0001). Salt-deprived and high-salt diets (0.0035 and 4% NaCl, respectively) were given to 16 and 18 additional controls, 9 and 7 2K,1C, and 7 and 7 1K,1C. Salt-deprived sham animals had greater endocardial and midwall shortening (106 +/- 7 and 111 +/- 10% of predicted, both P < 0.002) than sham rats on 0.4% NaCl, whereas 4% NaCl had no effect. Five of sixteen salt-deprived sham rats had supranormal observed-to-predicted midwall shortening ratios for LV chamber size, suggesting an enhanced inotropic state. Salt-deprived and high-salt diets had negligible effects on LV performance in Goldblatt rats. Thus use of midwall shortening reduces the number of renovascular hypertensive rats with apparently increased LV function. Salt deprivation stimulates LV myocardial function in normal rats independent of chamber dimension (i.e., an indirect measure of preload) but does not influence LV performance in Goldblatt hypertension 8 wk after renal artery clipping.

Animals↗
PubMed1996

[Surgical treatment of ovarian cysts: economic analysis as a means for the evaluation of alternative technics. Results of a biennial study].

The large use of new gynaecological technologies such as the operative laparoscopy, requires both efficacy and efficiency evaluation. The aim of this work is to compare costs of the surgical treatment of ovarian cysts between two groups of patients--35 patients undergone to laparotomic cystectomy (age: mean 27.5) and 34 operated by laparoscopic technique (age: mean 27). The analysis of the costs, related to three steps of health care (pre-operative, operative, post-operative) shows that the laparoscopic cystectomy results the more efficient intervention (L. 6,244,808 vs L. 8,310,002). This economic analysis may offer a planning tool for health care to hospital managers and represent an efficiency evaluation criterion of surgical techniques employed by the gynaecologists.

Adult↗
PubMed1995

Radionuclide monitoring of cardiac adaptations to volume loading in patients with dilated cardiomyopathy and mild heart failure. Effects of angiotensin-converting enzyme inhibition.

BACKGROUND: Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction. METHODS AND RESULTS: Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction < 50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged. CONCLUSIONS: Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.

Adult↗
PubMed1995

Transition from asymptomatic left ventricular dysfunction to congestive heart failure.

One of the main goals of modern management and care of heart failure is to prevent the disease to progress toward congestion and death. The achievement of such an objective may, in fact, guarantee a sufficient quality of life and reduce the exposure of patients to the most common life-threatening complications associated with the congestive stage of the disease. Early identification of left ventricular dysfunction as well as a better knowledge of the mechanisms that favor the progression to more advanced stages of heart failure are fundamental requirements for the proper treatment of asymptomatic heart failure and for preventing the transition to symptomatic and more severe heart failure. The authors reviewed the literature on this topic, with emphasis on a series of studies they performed, to characterize the pathophysiologic profile of mild heart failure and the mechanisms that are possibly involved in the progression to congestive heart failure.

Adaptation, Physiological↗
PubMed1995

Regulation of 11 beta-hydroxylase cytochrome p450 expression by cholesterol in spontaneously hypertensive rats.

OBJECTIVE: To investigate whether hypercholesterolaemia interferes with the expression of the enzymes involved in steroid biosynthesis in the adrenal cortex. METHODS: Twenty-four 5-week-old male spontaneously hypertensive rats (SHR) were randomly assigned to a high (1%) cholesterol diet (n = 8) or to a matched cholesterol-free diet (n = 8) for 6 weeks. A third group (n = 8) was studied after 2 weeks of washout from the high-cholesterol intake. A cohort of age- and sex-matched normotensive Wistar-Kyoto (WKY) rats (n = 24) underwent the same treatments and was used as a control. RESULTS: In SHR cholesterol feeding reduced urinary sodium excretion (0.8 +/- 0.1 versus 1.4 +/- 0.1 mmol/24 h in the cholesterol-free group), increased plasma aldosterone levels (299 +/- 60 versus 154 +/- 24) and reduced plasma corticosterone levels (142 +/- 21 versus 278 +/- 35 ng/ml). Those responses were associated with a reduction of 11 beta-hydroxylase cytochrome P450 messenger RNA (mRNA) in the adrenal cortex (-52.3 +/- 3.4%) whereas aldosterone synthase mRNA remained unchanged. That effect and the changes in electrolyte excretion and steroid levels were no longer detectable after withdrawal of the diet. In WKY rats high-cholesterol diet induced no significant changes in urinary electrolyte excretion, steroid levels and expression of 11 beta-hydroxylase cytochrome P450 and aldosterone synthase in the adrenals. CONCLUSIONS: The present results indicate that in SHR hypercholesterolaemia selectively interferes with the adrenal steroid biosynthetic pathway by reducing the expression of 11 beta-hydroxylase, leading to accumulation of mineralocorticoids and sodium retention.

Adrenal Cortex↗
PubMed1995

Influence of O2 deprivation, reduced flow, and temperature on release of ANP from rabbit hearts.

The separate effects of hypoxia and ischemia on atrial natriuretic peptide (ANP) release were evaluated in Langendorff-perfused rabbit hearts. Heart rate, coronary flow, and atrial and ventricular volumes were kept constant. Hypoxia was induced for 20 min at room temperature in seven hearts and at 37 degrees C in a second group of seven hearts. A third group of eight hearts was subjected to global ischemia for 20 min by reducing coronary flow to 1 ml/min at room temperature. All hearts were reoxygenated/reperfused at 37 degrees C for 30 min. Hypoxia at 37 degrees C induced a significant increase in ANP release. In contrast, both room temperature hypoxia and ischemia were characterized by a significant decrease in ANP release, despite hemodynamic alterations similar to those recorded during hypoxia at 37 degrees C. Both reoxygenation and reperfusion induced a prompt reversal of the changes of ANP release observed during the period of oxygen deprivation. These data demonstrate that decreased oxygen availability and reduced coronary flow are not the primary factors affecting release of ANP during ischemia and that alterations of myocardial temperature may play a major role in this phenomenon.

Animals↗
PubMed1995

Regulation of aldosterone biosynthesis by adrenal renin is mediated through AT1 receptors in renin transgenic rats.

The transgenic (TG) rat (mREN2)27 is characterized by overexpression of the additional mouse Ren-2d gene in the adrenal cortex with marked suppression of renal renin. We have previously shown that in salt-depleted TG rats enhanced activation of mineralocorticoid biosynthesis is associated with selective stimulation of adrenal renin. To investigate whether the local renin-angiotensin system regulates aldosterone biosynthesis in the adrenal cortex of TG rats, we studied the effects of the AT1-angiotensin subtype receptor antagonist DuP 753 on aldosterone production in 5-week-old TG rats during salt restriction. All the rats (n = 56) were shifted from regular chow to a diet containing only 0.04% NaCl for 1 week. The AT1-receptor antagonist DuP 753 (10 mg/kg per day in drinking water) was administered to 27 of these rats during low-salt diet. Subgroups of rats were killed at 0,4, and 7 days. Low-salt diet increased both adrenal renin activity (from 31 +/- 3 to 77 +/- 4 and 85 +/- 2 ng angiotensin I.h-1.mg protein-1 at 4 and 7 days, respectively; P < .001) and mRNA (by 68.4 +/- 10% and 80 +/- 17% from baseline, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1995

Rilmenidine in patients with left ventricular hypertrophy: beyond the reduction of left ventricular mass.

It is generally accepted that the development of left ventricular hypertrophy (LVH) represents a multifactorial phenomenon that also involves neurohormonal mechanisms. This finding may account for the ability of angiotensin-converting enzyme inhibitors to induce faster and more complete reversal of LVH than that observed with other antihypertensive treatments. The sympathetic system is also involved in the genesis of hypertension-induced LVH. We assessed the effects of satisfactory long-term treatment with rilmenidine, a new oxazoline with a potent antihypertensive action, on cardiovascular structural abnormalities and cardiac endocrine function in hypertensive patients with left ventricular hypertrophy. Eleven patients underwent M-mode and two-dimensional Doppler echocardiography, peripheral pulsed Doppler flowmetry, determination of plasma atrial natriuretic factor [(ANF) pg/ml] and renin activity, and 24-h urine electrolyte excretion under control conditions, after 4 weeks of blood pressure normalization, after 1 year of satisfactory antihypertensive treatment and, finally, 4 weeks after therapy withdrawal. I.VH (g/m2 body surface area) was reversed after 1-year treatment (from 152 +/- 5 to 131 +/- 4, p < 0.05). One-year treatment induced an improvement in brachial artery compliance (cm4/dyne.10(7)) (from 0.92 +/- 0.06 to 1.16 +/- 0.08, p < 0.05) that persisted after withdrawal of treatment (1.17 +/- 0.06, p < 0.05). Plasma renin activity and urinary electrolyte excretion did not change throughout the study, whereas ANF remained unchanged after blood pressure normalization (48.4 +/- 6.2 versus 44.7 +/- 2.9, NS), fell after reversal of LVH (28.6 +/- 3.4, p < 0.05), and remained significantly lower than under control conditions after therapy withdrawal (27.5 +/- 2.9, p < 0.05). These results demonstrate that a satisfactory long-term antihypertensive treatment with rilmenidine is able to reverse cardiovascular structural changes and to restore cardiac endocrine function.

Antihypertensive Agents↗
PubMed1995

Animal models of genetic hypertension: what can we learn for human hypertension?

1. The dissection of the genetic components of common complex diseases, such as hypertension, represents a major investigational challenge. The use of inbred experimental animal models of the disease represents a time-honoured approach to reducing the difficulty of this task. 2. Recent progress in molecular genetics has raised expectations that the application of powerful new techniques to established animal models of hereditary hypertension may provide important new insights into the genetic basis of human hypertension and perhaps direct access to genes involved in human hypertension. 3. These methods provide exciting opportunities, but to recognize their full potential will require the revision of many traditional and established strategies used in hypertension research. There can be little doubt that these methods, if applied wisely, will make an important contribution to our understanding of hypertension as a disease that is the result of the interaction of genetic and environmental factors. 4. Whether the applicability of results obtained in experimental animals is primarily conceptual, furthering our understanding primarily of disease mechanisms, or whether newly recognized disease-relevant genes will directly identify their human homologues as being involved in the pathogenesis of hypertension in humans cannot be predicted with certainty. Either possibility fully justifies efforts and resources directed into the application of molecular genetic research to experimental animal models.

Animals↗