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Biomedical subjects

F Fischetti

Publications and source records attributed to F Fischetti.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ace inhibition in renal disease: risks and benefits.

The kidney is one of the principal target organs of hypertension and most diseases of the kidney are associated with blood pressure elevation. Studies in animal models of hypertensive renal disease have provided insights into the complex relationship between systemic and glomerular hypertension. The intrarenal renin-angiotensin system (RAS) appears to play an important role in the pathogenesis of progressive glomerular injury. Thus, angiotensin converting enzyme inhibitors (ACEi) may have a specific therapeutic advantage in the treatment of hypertension associated with progressive renal disease. However, in contrast to their possible renoprotective effect in diabetic nephropathy or in renal hypertension, there are increasing evidence that, in the presence of a reduction in renal perfusion, intrarenal haemodynamic effect of ACEi may lead to compromised renal function. ACEi appear to have dual effects on renal function depending on the setting in which they are administered.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Peripheral adrenoceptors in hypotension of hemodialyzed uremic patients.

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.

Adult↗
PubMed1991

[Regulation of platelet alpha2 adrenergic receptors in a population of patients with essential arterial hypertension and in normotensive subjects].

The development of specific binding techniques for the study of adrenergic receptors on circulating human blood cells has allowed a better understanding of the physiological alterations of adrenergic receptors and changes of adrenergic receptors in pathological conditions such as hypertension. Alpha adrenoceptors play an important part in blood pressure regulation at several sites. There are contradictory and conflicting reports on whether alpha receptor mechanisms are altered in essential hypertension. To address further the role of alpha 2 adrenoceptors in human essential hypertension the number and the affinity of alpha 2 adrenergic receptors and plasma catecholamine levels were measured in 20 normotensive and 24 hypertensive subjects. The median number of receptors (Bmax) was 159.10 +/- 14.38 fmol/mg protein for controls versus 179.09 +/- 13.26 fmol/mg protein for hypertensives. The median dissociation constant (KD) of the receptors for 3H-Yohimbine was 1.43 +/- 0.17 nmol/l for controls and 1.85 +/- 0.19 nmol/l for hypertensives patients. There were no differences in catecholamine plasma levels between the two groups. In controls platelet alpha 2 receptor number correlated with age (p less than 0.003) but not with blood pressure values. Our results show that measurement of platelet alpha 2 receptor levels and affinity is unable to differentiate a group of hypertensives from normotensives. Nevertheless, we cannot exclude a possible role of peripheral alpha 2 adrenergic receptors in the pathogenesis of high blood pressure.

Adult↗
PubMed1991

An ultrasonographic method to measure the sensitivity of the baroreflex in clinical practice: application to pharmacological studies.

To determine whether it is possible to assess baroreceptor sensitivity by measuring changes in blood velocity in the carotid artery and changes in the heart rate, we performed a series of 108 experiments in 19 hypertensives aged 20-57 years (mean 46.6 +/- 8.6). In each experiment, we took simultaneous measurements of carotid artery blood flow velocity (Doppler technique), the brachial intra-arterial blood pressure and the heart rate, during a rapid and transient increase in blood pressure induced by injections of phenylephrine. We then calculated the maximum slope of the regression lines correlating blood velocity with the heart period (Trieste method) and blood pressure with the heart period (Oxford method). We obtained good accuracy from the Trieste method compared with the Oxford method, as assessed by the mean of the sum of the squares (difference + 5%, NS). After the administration of 4 mg oral lacidipine to 13 essential hypertensives, aged 37-54 years (47.6 +/- 5.3), baroreflex sensitivity was not changed, as assessed by either method (Oxford method 10.1 +/- 5.5 versus 9.8 +/- 6.2 ms/mmHg; Trieste method - 0.57 +/- 0.32 versus - 0.49 +/- 0.31 ms/Hz). The coefficients of variation for the two methods, calculated for the measurements taken before and after the administration of lacidipine, were not statistically different (Oxford method 25.0 +/- 18.4 versus 36.2 +/- 16.0; Trieste method 36.7 +/- 19.2 versus 39.7 +/- 19.2). The new non-invasive Trieste method thus showed the same accuracy and precision as the invasive Oxford method in measuring baroreflex sensitivity and can be used in pharmacological studies.

Antihypertensive Agents↗
PubMed1990

[Activity and number of lymphocyte beta adrenergic receptors after protracted treatment with mepindolol sulfate of patients with essential arterial hypertension].

beta-Blockers are widely used in the treatment of high blood pressure. To study clinical and pharmacological role of beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA), lymphocyte beta 2-adrenoceptor density, assessed by 3H-dihydroalprenolol binding, was investigated in 10 hypertensive patients (8 male, 2 female) aged 20-62 years before and after treatment with mepindolol (5 mg o.i.d.). After 3 months of therapy, both systolic (from 169.7 +/- 28.3 mmHg to 146.5 +/- 17.6 mmHg) and diastolic (from 108.7 +/- 17.5 mmHg to 93.6 +/- 8.7 mmHg) blood pressure decreased significantly. Similarly heart rate decreased after treatment (from 76.5 +/- 10.1 b/min to 62.7 +/- 3.4 b/min). Mepindolol treatment decreased beta 2-adrenoceptor density from 1112.2 +/- 459.6 sites/cell to 295.1 +/- 131.2 sites/cell. Plasma noradrenaline values did not correlate with lymphocyte beta 2-receptor number both before and after treatment. Our results show that ISA may play an important role in modulating beta 2-adrenoceptor density on lymphocyte surface. This biological effect could be relevant in reducing the so called "propranolol rebound effect".

Adult↗
PubMed1989

Effects of amlodipine on renal hemodynamics.

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. This study examined the effects of the novel dihydropyridine amlodipine on the hemodynamic response of the isolated perfused kidney to angiotensin II. Amlodipine completely reversed the angiotensin II-induced decrement in glomerular filtration rate of this model (0.72 +/- 0.15, 0.26 +/- 0.10 and 0.73 +/- 0.12 ml/min/g for control, angiotensin II and angiotensin II plus 0.1 microM amlodipine respectively). In contrast, amlodipine only partially restored renal perfusate flow (35.8 +/- 2.7, 14.7 +/- 1.9 and 23.7 +/- 2.5 ml/min/g for control, angiotensin II and angiotensin II plus amlodipine), thereby increasing filtration fraction. These findings are consistent with previous observations from this laboratory indicating that dihydropyridines predominantly vasodilate preglomerular renal resistance vessels and through this mechanism exert a preferential augmentation of glomerular filtration rate.

Amlodipine↗
PubMed1989

Regional hemodynamic effects of slow-release nicardipine in elderly patients with hypertension: evaluation by a new ultrasound technique.

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.

Aged↗
PubMed1989

Reduction of blood pressure in obese hyperinsulinaemic hypertensive patients during somatostatin infusion.

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.

Adult↗
PubMed1988

Platelet alpha 2-adrenoceptor modifications induced by long-term treatment with indapamide in essential hypertension.

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.

Adult↗
PubMed1988

Acute effects of intravenous infusions of alcohol on baroreceptor sensitivity in essential hypertension.

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)

Adult↗
PubMed1988

Arterial compliance and baroreceptor sensitivity after chronic treatment with indapamide.

Arterial compliance, assessed by the ratio of stroke volume to pulse pressure, and baroreceptor sensitivity (Oxford method), were determined in ten patients with essential hypertension, treated with placebo or indapamide (2.5 mg/day), in a cross-over, single blind study. After three months of therapy, mean arterial pressure was significantly reduced from 127 +/- 10 to 118 +/- 9 mmHg, (P less than 0.001), as was total peripheral vascular resistance (from 3017 +/- 561 to 2457 +/- 614 dyne/sec/cm-5/m2, P less than 0.001). Significant increases occurred in cardiac index (3.47 +/- 0.55 to 4.03 +/- 0.86 l/min/m2, P less than 0.01), baroreceptor sensitivity assessed with phenylephrine (from 11.69 +/- 7.9 to 15.0 +/- 9.1 msec/mmHg, P less than 0.01) or with nitroglycerine (from 4.77 +/- 1.6 to 7.11 +/- 2.7 msec/mmHg, P less than 0.01) and arterial compliance (from 1.27 +/- 0.42 to 1.55 +/- 0.57, P less than 0.01). A significant direct correlation was found between arterial compliance and baroreceptor sensitivity assessed during induced increase and reduction of BP, both during placebo (r = 0.88, P less than 0.001 and r = 0.77, P less than 0.01, respectively) and during active therapy (r = 0.94, P less than 0.001 and r = 0.92, P less than 0.001, respectively). These results support the conclusion that chronic treatment with indapamide enhances arterial compliances and reduces the heart load and blood vessel stress. The same effect could explain the enhancement of baroreceptor sensitivity promoted by the drug.

Adult↗
PubMed1986

Antihypertensive activity of arylidenaminoguanidine derivatives.

The synthesis of new benzylidenaminoguanidine compounds is described. Some of these compounds were tested for antihypertensive activity in conscious unrestrained spontaneously hypertensive rats. The compounds examined possess a significant antihypertensive activity, qualitatively different from that of clonidine. For the tested compounds, the absence of the transient rise in blood pressure, which appears immediately after administration of clonidine-like drugs, is noteworthy.

Animals↗
PubMedDate not supplied

Complement-endothelial cell interactions: pathophysiological implications.

The function of the endothelial cells can be modulated by humoral factors present in the circulation and in the extravascular fluid, including proteins of the complement system. This review examines the multiple interactions between the complement system and the endothelial cells and their functional consequences on inflammation, coagulation and regulation of vascular tone. The implications of these interactions in the induction and progression of the vascular lesions occurring in atherosclerosis, ischemia/reperfusion and xenotransplantation and the possible therapeutic approaches in terms of complement regulation are also discussed.

Animals↗