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Biomedical subjects

P Bolli

Publications and source records attributed to P Bolli.

At least 19 recordsLinked to original sources
PubMed1991

Temperature-dependence of LDL binding and activation of human platelets.

The effect of low density lipoprotein (LDL) on intracellular free calcium ion concentration ([Ca2+]i), taken as an index of the degree of platelet activation, was investigated in normal volunteers. At 37 degrees C LDL, in a dose of 20 micrograms of protein/ml, increased [Ca2+]i in all subjects tested (basal 57 +/- 11 to 113 +/- 19 nM). In contrast, when measurements were performed at 20 degrees C, no effect on [Ca2+]i was seen following LDL. Thrombin (0.2 U/ml) increased [Ca2+]i to 455 +/- 98 nM. When platelets had been exposed to LDL before thrombin stimulation, this increase was less pronounced (to 301 +/- 43 nM). Our finding of a temperature dependence of LDL induced increase in platelet [Ca2+]i supports the concept of a platelet-LDL receptor mediated mechanism. Furthermore, the lower thrombin response following LDL exposure suggests a LDL-thrombin interaction, possibly at the thrombin receptor level and/or calcium recruitment from the same stores.

Adult↗
PubMed1991

Once- vs. twice-daily nitrendipine in the treatment of mild to moderate hypertension, Canadian Nitrendipine Study Group.

Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Effectiveness and tolerability of once versus twice daily nitrendipine in the treatment of mild to moderate hypertension. The Canadian Nitrendipine Study Group.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

Blood Pressure↗
PubMed1990

Smoking, antihypertensive treatment benefit, and comprehensive antihypertensive treatment approach: some thoughts on the results of the International Prospective Primary Prevention Study in Hypertension.

Several major studies investigated the possibility of a primary preventive effect of beta-blockers. The International Prospective Primary Prevention Study in Hypertension (IPPPSH) compared a beta-blocker-containing vs. a non-beta-blocker-containing antihypertensive regimen in 6,357 moderate-severe hypertensive men and women treated over 3-5 years. Blood pressure (BP) control was comparable with either regimen. beta-Blocker treatment was associated with less hypokalemia, earlier electrocardiogram normalization, and fewer withdrawals for uncontrolled hypertension. In agreement with the Medical Research Council (MRC) trial on mild hypertension and the Heart Attack Primary Prevention in Hypertension (HAPPHY) trial, but at variance with the Primary Prevention Metoprolol in Patients with Hypertension (MAPHY) study, cardiac event rates were similar in beta-blocker- and non-beta-blocker-treated patients. With either regimen, in-study BP reduction was associated with a lower rate of stroke as well as of cardiac events. In a subgroup analysis, nonsmokers appeared to derive beta-blocker benefit, the results being similar to those of the MRC. Smokers required higher doses of drugs to achieve diastolic target pressure, had a higher heart rate and hematocrit, and a higher cardiac event rate than nonsmokers at any given level of diastolic pressure. Except for the MAPHY trial, these primary prevention studies do not support the concept of a cardiac primary preventive effect of antihypertensive beta-blockade but stress the importance of good BP control and a comprehensive risk factor prevention approach in the management of hypertensive patients.

Adrenergic beta-Antagonists↗
PubMed1990

The 24 h blood pressure responses of hypertensives to a once-a-day cilazapril regimen.

The efficacy of once-a-day cilazapril (a new long acting converting enzyme inhibitor) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated. Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were randomly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25, 2.5 or 5.0 mg/day for a further four weeks. At the end of weeks 4 and 8, systolic and diastolic blood pressures and heart rates were recorded, supine and standing, at 0, 2, 4, 6, 9, 12 and 24 h following a single dose of drug. At the same times, blood was withdrawn for determination of plasma renin activity and aldosterone. Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day. Supine and erect heart rates were unchanged with respect to drug dosage, and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups. Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion. There were no changes in resting aldosterone, but plasma renin activity was increased at all drug dosages. A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period. Cilazapril does not appear to interfere with the reflex autonomic responses to postural change.

Adult↗
PubMed1990

Relations between sympathetic activation and plasma atrial natriuretic factor in man.

To study the relationship between sympathetic activation and cardiac release of atrial natriuretic factor in man, plasma concentrations of norepinephrine, epinephrine and atrial natriuretic factor were measured in 20 patients before and after dynamic exercise (16 subjects) or the application of venous occlusion cuffs to the thighs (4 subjects). Plasma concentrations of norepinephrine, epinephrine and atrial natriuretic factor all increased during exercise, whereas venous occlusion produced a fall in plasma atrial natriuretic factor. There was no relation between basal plasma concentrations of atrial natriuretic factor and either norepinephrine or epinephrine. However, there was a linear relation between the changes in plasma atrial natriuretic factor induced by exercise or thigh cuffs and both plasma norepinephrine (r = 0.829, p less than 0.0001) and epinephrine (r = 0.733, p less than 0.001). We conclude that, in man, acute changes in sympathetic activity and release of atrial natriuretic factor are closely related. Further studies are required to determine whether this association is due wholly to the hemodynamic effects of sympathetic activation, or whether the latter has a direct effect on the release of atrial natriuretic factor.

Atrial Natriuretic Factor↗
PubMed1989

Comparative effects of haemodialysis and haemofiltration on plasma atrial natriuretic peptide.

The effects of 4 h haemodialysis (15 patients) or 4 h haemofiltration (five patients) on plasma concentrations of atrial natriuretic peptide (ANP) were compared by means of a sensitive radioreceptor binding assay, and related to accompanying changes in body weight, blood pressure and plasma renin activity. Before dialysis, plasma ANP concentrations were considerably elevated: haemodialysis group 10-484 pmol/l (mean 156 pmol/l); haemofiltration group 72-320 pmol/l (mean 170 pmol/l). Although plasma concentrations of ANP fell markedly with treatment in both groups: post-haemodialysis 2-187 pmol/l (mean 67 pmol/l); post-haemofiltration 47-135 pmol/l (mean 79 pmol/l), after treatment it remained above the normal range in 14 of the 20 patients. Pretreatment plasma ANP was related to systolic blood pressure (r = 0.459; P less than 0.05) but bore no relationship to mean or diastolic blood pressure, or plasma renin activity. The fall in plasma ANP concentration during treatment correlated with the postural blood pressure drop after dialysis (r = 0.505; P less than 0.05), but was unrelated to changes in weight or plasma renin activity with haemodialysis or haemofiltration. Plasma ANP concentrations rose rapidly again in the 60 min after dialysis treatment, without change in body weight. These results show that high levels of biologically active ANP circulate in end-stage renal disease. The fact that these are not reduced to normal by haemodialysis or haemofiltration, despite restoration to normovolaemic or hypovolaemic state, suggests that the increased levels of ANP in end-stage renal failure are due to both hypervolaemia and other factors, which may include occult cardiac dysfunction and loss of renal clearance.

Adult↗
PubMed1989

The vasodilating effect of atrial natriuretic peptide in normotensive and hypertensive humans.

Atrial natriuretic peptide (ANP) infused intra-arterially into the forearm results in a dose-dependent vasodilator response of rapid onset. The maximal forearm vasodilator response to ANP amounts to about 60% of the maximal forearm vasodilator response to sodium nitroprusside and combined infusion of ANP and sodium nitroprusside has an additive vasodilator effect. ANP-induced vasodilation is greater than that of postjunctional alpha 1- or alpha 2-adrenoceptor blockade or of beta 2-adrenoceptor stimulation but is smaller than due to calcium entry blockade. ANP-induced vasodilation can easily be overcome by norepinephrine and to a lesser extent by angiotension II (Ang II). The similarity of the dose-response relationships for vasodilation and for natriuresis suggests that ANP may be equally effective on its renal and vascular targets. In patients with essential hypertension, intra-arterial infusion of ANP produced a greater vasodilator response than in normotensives and this was inversely related to plasma renin activity, suggesting greater vasodilator responsiveness to ANP in low-renin hypertension. ANP caused vasodilation in humans but this may become less apparent when ANP is infused into the systemic circulation because of cardiovascular sympathetic reflex mechanisms blunting ANP vasodilation. Although the role of ANP in circulatory disease states is unclear, it appears that it could serve a physiological function as an endogenous vasodilator (and natriuretic) principle for volume homeostasis in humans.

Atrial Natriuretic Factor↗
PubMed1989

Mechanisms of action and clinical use of calcium antagonists in hypertension.

Calcium antagonists are potent arterial vasodilators that do not lead to relevant chronic sympathetic reflex activation and sodium and volume retention. This favorable hemodynamic profile renders them suitable for monotherapy of hypertension in which they can reduce the calcium influx-dependent functional component of elevated vascular resistance that may be enhanced by altered vascular muscle cation handling and increased intracellular free calcium concentrations. Clinical studies have proved their efficacy, safety, and good tolerability alone or in combination with other drugs in uncomplicated hypertension in which they are particularly effective in older, low renin, and possibly, black patients. These properties and their efficacy in the treatment of severe and accelerated hypertension or hypertensive emergencies make them a valuable addition to already available drug therapy.

Animals↗
PubMed1989

Bevantolol attenuates thiazide stimulated renin secretion and catecholamine release in diuretic resistant hypertensives.

An attempt was made to establish whether cardioselective beta-blockade could counteract the stimulation by hydrochlorothiazide of the renin-angiotensin and sympathetic nervous systems and to what extent such actions contributed to the antihypertensive effect of bevantolol. The hemodynamic and neurohumoral responses of 21 thiazide resistant hypertensives who had received sequential chronic therapy with hydrochlorothiazide, hydrochlorothiazide combined with bevantolol and bevantolol monotherapy were compared. In these patients, bevantolol had a negative chronotropic effect and appeared, when administered alone, to induce an overall lowering of sympathetic nervous system activity without inhibiting the reflex responses of peripheral vascular resistance to postural change or lowered heart rate. When bevantolol and hydrochlorothiazide were administered together, sympathetic activity appeared to be maintained, possibly as a reflex response to volume depletion but vascular resistance did not appear to be responsive to baroreceptor stimulation. Diminished vascular reactivity induced by the hydrochlorothiazide is suspected to be a contributory factor. Inhibition of thiazide stimulated renin release by bevantolol may contribute to the antihypertensive effect of the combined therapy.

Adrenal Glands↗
PubMed1988

Impact of smoking on heart attacks, strokes, blood pressure control, drug dose, and quality of life aspects in the International Prospective Primary Prevention Study in Hypertension.

Effects of smoking are highlighted in a posthoc analysis of this randomized, double-blind International Prospective Primary Prevention Study in Hypertension (IPPPSH). At the time of entry, 37% of the men and 23% of the women were smoking cigarettes, and only 537 patients changed their smoking status during the trial. In men and women, smoking doubled cardiac and cerebrovascular event rates. Nonsmoking men had fewer myocardial infarctions and sudden deaths when treated with oxprenolol. Smoking status did not affect in-study blood pressure control, the type of drugs, or the combinations used, but smokers were given higher doses of oxprenolol. For a given blood pressure during antihypertensive treatment, rates for cardiac and cerebrovascular events were higher in smokers. Heart rates were higher in both oxprenolol and non-beta-blocker-treated smokers. Smoking dose dependently increased hematocrit level. Among physician-elicited symptoms, dyspnea and cold extremities were more frequent in smokers, whereas dyspnea, headaches, impotence, dizziness, and anxiety states were common, with unsatisfactory blood pressure control (diastolic blood pressure greater than 95 mm Hg). Quality of life may be more jeopardized by smoking, poor blood pressure control, or diuretic use than by beta-blocker-based therapy. In the IPPPSH, the patient who smoked had double the cardiovascular complication rates without cardiac benefit from the beta-blocker despite higher doses given; the higher heart rate and hematocrit level may have been contributing factors.

Adrenergic beta-Antagonists↗
PubMed1988

Modulation of left ventricular hypertrophy by dietary salt and inhibition of angiotensin converting enzyme.

The interactions of blood pressure, salt intake and angiotensin converting enzyme (ACE) inhibition were investigated in the Dahl salt-sensitive (DS) and salt-resistant (DR) strains of rats. Eight-week-old DS and DR (40 of each) were separately randomized to receive a low- (0.4% NaCl) or a high- (8% NaCl) salt diet for 3 weeks. Thereafter the rats were further separated randomly to receive the ACE inhibitor lisinopril (3-8 mg/kg per day) or no drug treatment for 11 weeks. In untreated DS rats blood pressure rose, paralleled by a higher left ventricular mass (ratio left ventricular weight/body weight) irrespective of salt intake. Lisinopril lowered blood pressure to normotensive levels in all groups except DS rats on a high-salt diet, despite doses of up to 100 mg/kg per day, although there was a significant fall in blood pressure. Lisinopril reduced left ventricular mass significantly on the low- but not on the high-salt diet. Plasma renin activity increased on lisinopril treatment in all groups except DS rats on the high-salt diet. Regression of an increased left ventricular mass by ACE inhibition seemed to be impaired by a high salt intake, even when blood pressure was lowered. Therefore, although for regression of left ventricular hypertrophy, reduction of afterload was the leading factor, this might be adversely affected by a high salt intake.

Aldosterone↗
PubMed1988

Hemodynamic and counterregulatory effects of calcium antagonists in hypertension.

Increased systemic vascular resistance in essential hypertension depends on increased calcium influx. Calcium antagonists lower cytosolic free calcium concentrations mainly through a reduction of transmembraneous calcium influx and are potent arterial vasodilators. Dihydropyridine calcium antagonists are pharmacologically more potent with respect to arterial vasodilatation than verapamil- or diltiazem-type calcium antagonists and have less or no clinically detectable negative inotropic effects, but this seems to be of importance only in patients with reduced cardiac function. All calcium antagonists lower high blood pressure through a reduction of elevated systemic vascular resistance without clinically relevant activation of sympathetic reflexes or the renin-angiotensin-aldosteron system. However, subtle changes of sympathetic nervous system activity may codetermine the acute and chronic blood pressure response. They do not lead to volume retention because of improved intrarenal hemodynamics and a diuretic effect. Interference with angiotensin and sympathetically mediated vasoconstrictor mechanisms probably also contributes to their antihypertensive effect. This hemodynamic profile is similar for all calcium antagonists but the degree of acute sympathetic stimulation seems to be greater for dihydropyridines. Their overall favorable hemodynamic and neurohumoral profile and their proven efficacy and lack of serious side effects have made calcium antagonists a valuable addition to the armanentarium available for monotherapy of hypertension.

Animals↗
PubMed1987

The vasodilator potency of atrial natriuretic peptide in man.

The vasodilating potency of alpha-human atrial natriuretic peptide (alpha-hANP) was investigated in the forearms of 16 normotensive subjects, 22 to 48 (mean 28) years old, with the use of venous occlusion plethysmography. alpha-hANP, 0.005 to 1.5 micrograms/min/100 ml forearm volume (FAV), infused in nine dose steps into the brachial artery increased forearm blood flow (FAF; ml/min/100 ml FAV) from 2.8 +/- 0.4 (SEM) to a maximum of 9.6 +/- 1.1. Forearm vascular resistance (mean arterial pressure/FAF) decreased by 72%. The alpha-hANP dose that produced a 50% vasodilator response was 0.093 +/- 0.016 microgram/min/100 ml FAV (n = 11) and it resulted in a venous plasma concentration of ANP (pANP) of 115 +/- 7 pmol/liter (normal 2 to 80; radioreceptor assay). Intraindividually, the maximum dose of alpha-hANP induced an increase in FAF that was 60% of the maximum response to sodium nitroprusside (14.1 +/- 1.8). Combined infusions (n = 9) of maximum forearm vasodilator doses of alpha-hANP and nitroprusside increased FAF to 22.7 +/- 3.4; this additive vasodilator effect of alpha-hANP and nitroprusside is consistent with their different actions on the guanylate cyclase system. In man, the direct vasorelaxant effect of alpha-hANP occurs at concentrations within the upper normal range of pANP, suggesting a physiologic vasodilator role for alpha-hANP.

Adult↗
PubMed1987

Mechanisms of action of calcium antagonists in hypertension.

Cytosolic free calcium concentrations determine the magnitude of tension development of smooth muscle cells and are pivotal for regulation of vascular smooth muscle tone and systemic vascular resistance. Elevated free calcium concentrations have been found in platelets from hypertensive patients, and platelet free calcium concentration, possibly an index of vascular smooth muscle cell free calcium concentration, correlated with blood pressure in normotensive and hypertensive subjects. Increased systemic vascular resistance in essential hypertension depends on increased calcium influx. Calcium antagonists lower cytosolic free calcium concentrations mainly through a reduction of transmembraneous calcium influx and are potent arterial vasodilators. High blood pressure is lowered through a reduction of elevated systemic vascular resistance but, in contrast to other direct acting vasodilators, without clinically relevant sympathetic reflex activation. However, subtle changes of sympathetic nervous system activity may codetermine the acute and chronic blood pressure response. Calcium antagonists do not lead to volume retention, because of improved intrarenal hemodynamics and a diuretic effect. Interference with angiotensin and sympathetically mediated vasoconstrictor mechanisms probably also contributes to their antihypertensive effects. This favorable hemodynamic profile renders calcium antagonists suitable for monotherapy of uncomplicated hypertension where they are particularly effective in older patients and also for the therapy of hypertensive crisis.

Blood Platelets↗
PubMed1986

Calcium antagonists and the second drug for hypertensive therapy.

Calcium antagonist monotherapy is more effective in older patients and in those with low plasma renin activity, whereas beta blockers control blood pressure better in younger patients and in those with normal or high renin activity. Monotherapy with a calcium antagonist has been shown to result in the reduction of diastolic blood pressure to equal to or less than 95 mm Hg in more than 80 percent of patients with essential hypertension. We investigated the antihypertensive efficacy of verapamil plus an angiotensin converting enzyme inhibitor and nifedipine plus a beta blocker in 24 patients (aged 41 to 68) with moderate to severe hypertension in whom monotherapy with a calcium antagonist had been ineffective. Blood pressure recorded in patients during the placebo period was 175 +/- 3/111 +/- 2 mm Hg (mean +/- SEM). Twelve patients received monotherapy with nifedipine (50.0 +/- 5.2 mg per day) and 12 others received verapamil (460 +/- 20 mg per day); neither treatment resulted in the reduction of diastolic blood pressure to less than 90 mm Hg. However, this goal was achieved when atenolol (89.5 +/- 25.7 mg per day) was added to the regimen of patients receiving nifedipine and enalapril (29.5 +/- 5.0 mg per day) was added to the regimen of those receiving verapamil; resultant blood pressures were 127 +/- 3/83 +/- 2 mm Hg and 137 +/- 5/85 +/- 1 mm Hg, respectively. It is suggested that in patients in whom hypertension is inadequately controlled by calcium antagonist monotherapy, counter-regulatory mechanisms can be blocked by the addition of a beta blocker or an angiotensin converting enzyme inhibitor to the calcium antagonist regimen, resulting in greatly improved, simple, well-tolerated, and safe control of blood pressure.

Adrenergic beta-Antagonists↗