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Biomedical subjects

P Bolli

Publications and source records attributed to P Bolli.

At least 37 records · Page 2Linked to original sources
PubMed1988

Fura-2 used as a probe to show elevated intracellular free calcium in platelets of Dahl-sensitive rats fed a high salt diet.

Elevated intracellular free calcium concentration [Ca2+]i in vascular smooth muscle cells has been implicated in the pathophysiology of hypertension. Platelet [Ca2+]i was measured using the fluorescent indicator, Fura-2, in Dahl sensitive (DS) and resistant (DR) rats given high (8% NaCl) and low (0.4% NaCl) salt diets, as well as in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The aim of this study was to show whether [Ca2+]i is elevated in salt induced hypertension. Platelet [Ca2+]i and systolic blood pressure (SBP) were higher (p less than 0.001) in DS rats given a high than low salt diets. In contrast, no changes in platelet [Ca2+]i and SBP were observed in DR rats. In SHR, platelet [Ca2+]i and SBP were higher (p less than 0.001) than in the WKY rats. Platelet [Ca2+]i correlated with SBP in all groups of rats (r = 0.929; p less than 0.001, n = 38). The parallel increase in SBP and [Ca2+]i in the DS high salt rats and the SHR suggests that an increased [Ca2+]i is involved in the pathophysiology of hypertension in the two models which differ with respect to the pathogenesis of their hypertension. This increase in [Ca2+]i therefore seems to reflect an abnormality in [Ca2+]i handling in hypertension regardless of its cause.

Animals↗
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↗
PubMed1988

Can plasma catecholamine levels be a useful index of sympathetic nervous system activity?

The hemodynamic responses of the sympathetic nervous system to the Valsalva maneuver were related to changes in circulating levels of catecholamines, aldosterone and plasma renin activity. Fourteen healthy normotensives (aged 27 +/- 8 years) took part. A catheter was inserted in the forearm then the subject was rested quietly (supine) for 30 mins. The Valsalva maneuver was performed (duration 40 s, intrathoracic pressure 40 mmHg) with continuous recording of supine heart rate. Blood was sampled before the maneuver (basal state) and at the bradycardic post maneuver phase for measurement of plasma noradrenaline, adrenaline, renin activity and aldosterone. In six subjects the procedure was repeated for durations of 10, 20, 30 and 40 s with a 30-min rest between each maneuver. Plasma catecholamines increased consistently (P less than 0.001) from pre- to post bradycardic phases of the maneuver. No changes in plasma renin activity or aldosterone were observed. The maximum tachycardia observed during each maneuver and the increments in catecholamine concentrations were each linearly related to the duration of straining but there was no overall correlation between the tachycardia and catecholamine concentrations. In conclusion under controlled conditions, plasma catecholamine concentrations can be useful indices of the stimulation of the sympathetic nervous system; the Valsalva maneuver does not appear to affect significantly the peripheral renin-angiotensin system; and the heart rate response to the Valsalva maneuver does not appear to be mediated solely by the sympathetic nervous system.

Adult↗
PubMed1987

Calcium antagonist induced vasodilation in peripheral, coronary and cerebral vasculature as important factors in the treatment of elderly hypertensives.

Increased arteriolar tone is the pathophysiological hallmark of essential hypertension and is determined by the intracellular free calcium concentration in the vascular smooth muscle cell. Calcium influx is an important determinant of vasoconstriction and excess calcium influx-dependent vasoconstriction has been shown by plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower BP by reducing calcium influx, calcium concentration and peripheral resistance. The degree of the attendant sympathetic nerve reflex activation and counter-regulatory mechanisms determines the antihypertensive response of the individual. Chronic monotherapy with a calcium antagonist results in an antihypertensive response, which is directly related to the patient's age and pretreatment BP and indirectly related to plasma renin levels. The resulting reduction in after-load neither leads to reduced cerebral blood flow in hypertensive patients, nor aggravates congestive heart failure. Calcium antagonists are a useful alternative to diuretics, primarily in older patients with low renin levels, either alone or combined with any other antihypertensive drug, and provide effective and safe control of blood pressure.

Aged↗
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

Electrocardiographic changes during antihypertensive therapy in the International Prospective Primary Prevention Study in Hypertension.

In the International Prospective Primary Prevention Study in Hypertension, electrocardiographic changes before and during 3- to 5-year antihypertensive treatment were investigated in a cohort of 5819 men and women aged 40 to 64 years with entry diastolic blood pressures of 100 to 125 mm Hg. They were randomly allocated to treatment regimens that either included or excluded the slow-release beta-blocker oxprenolol. Electrocardiograms (ECGs) were assessed using the Minnesota Code and assigned to groups of normal ECGs or ECGs with pressure-related, ischemic, "intermediate," or "other" abnormalities. Antihypertensive treatment was associated with a decrease (mainly in men) of pressure-related and (mainly in women) of intermediate abnormalities. Ischemic abnormalities increased, particularly in men. Inclusion of the beta-blocker resulted in a greater reduction in intermediate abnormalities and in a lesser increase in ischemic abnormalities. Better blood pressure control was associated with a lesser increase in ischemic abnormalities and in a regression of pressure-related abnormalities. The presence of ST segment depression and of a complete left bundle branch block in the entry ECG was associated with a significant risk for sudden death and myocardial infarction. Optimal blood pressure control prevents pressure-induced cardiac target organ damage and, hence, heart failure, and may delay the progression of ischemic abnormalities. This tallies with the lower critical cardiac event rate associated with lower blood pressure that was observed in the same study.

Antihypertensive Agents↗
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↗
PubMed1987

Greater vasodilator responsiveness to atrial natriuretic peptide in low-renin essential hypertensives.

Forearm vasodilator responses to atrial natriuretic peptide (ANP) were studied in twelve untreated patients with essential hypertension and twelve normotensive subjects. Alpha-human ANP (0.005 to 1.5 micrograms/min per 100 ml forearm volume) infused into the brachial artery increased forearm blood flow dose-dependently. This was paralleled by a decrease in forearm vascular resistance (FVR) which, at lower doses, was greater in essential hypertensives than in normotensives (P less than 0.001), and showed a lower ED50 for ANP in essential hypertensives (P less than 0.01). At higher doses of ANP the difference in vasodilator response between hypertension and normotension disappeared; the response to ANP was associated with a fall (P less than 0.01) in systemic blood pressure in hypertensives but not normotensives. At lower doses, the decreases in FVR were correlated directly with plasma renin activity in hypertensives (r = 0.656; P less than 0.05) but not normotensives. These data suggest greater vasodilator responsiveness to infusions of low doses of ANP in essential hypertensives, which is greater in low-renin states and blunted in high-renin states.

Adult↗
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↗
PubMed1986

Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure.

To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.

Adult↗
PubMed1986

Calcium antagonism--a new concept for treating essential hypertension.

Research on calcium antagonists has been prompted by the observation that the powerful vasodilatory effect of verapamil, as well as other calcium antagonists, is enhanced in hypertensive patients. Increased vascular resistance, seen in most types of hypertension, is determined by the intracellular free calcium concentration. The finding of an increased vascular responsiveness to calcium-channel blockade and the direct relation between the degree of antihypertensive response and the height of pretreatment blood pressure indicate abnormal intracellular calcium handling in patients with essential hypertension. This is supported by the observation that the intracellular free calcium concentration was significantly increased in patients with essential hypertension compared with normotensive subjects. The decrease in blood pressure with calcium antagonists was directly correlated with the patient's age and inversely with the pretreatment plasma renin activity. There was comparable antihypertensive efficacy among verapamil, nifedipine and nitrendipine. Increased understanding of pathophysiologic mechanisms in essential hypertension and pharmacotherapeutic studies have led to a new strategy for treatment of high blood pressure--in which calcium antagonists may be used, at least in part, as alternatives to diuretic drugs primarily in older and low renin patients with essential hypertension.

Age Factors↗
PubMed1986

Acute and chronic sympathetic reflex activation and antihypertensive response to nifedipine.

The importance of counterregulatory mechanisms triggered by arterial vasodilation for the antihypertensive response to the calcium entry blocking agent nifedipine was investigated in 13 men with mild to moderate essential hypertension. Blood pressure and systemic vascular resistance were significantly reduced 30 minutes after sublingual administration of 10 mg of nifedipine while heart rate, cardiac index and plasma norepinephrine concentrations increased (all p less than 0.01). Also, changes in mean blood pressure correlated inversely with arterial baroreflex sensitivity (r = -0.74, p less than 0.01), suggesting that arterial baroreflex mechanisms by means of sympathetic activation tend to limit the acute antihypertensive response. Blood pressure, but not systemic vascular resistance, decreased further (p less than 0.01) after 6 weeks of therapy with nifedipine 20 mg three times daily, while average heart rate, cardiac index and plasma norepinephrine concentrations had returned toward pretreatment values. Thus, a reduction of acutely increased sympathetic activity toward pretreatment values during long-term nifedipine therapy was associated with further decreases in blood pressure. The importance of sympathetic activity was also stressed by the finding of an inverse relation between chronic changes in heart rate and blood pressure (percent of control, r = -0.76, p less than 0.01). Blood volume did not change during long-term nifedipine therapy. The results suggest that the degree of sympathetic reflex activation in part determines the antihypertensive response to nifedipine monotherapy.

Adult↗
PubMed1986

Cardiac and vascular beta-adrenoceptor-mediated responses before and during treatment with bisoprolol or atenolol.

The degree of cardiac and vascular beta-adrenoceptor blockade of bisoprolol and atenolol was determined by the chronotropic dose 25 (CD25) of isoproterenol (the dose of an intravenous isoproterenol bolus required to increase resting heart rate by 25 beats/min) and by the increase in forearm blood flow (venous occlusion plethysmography) to intrabrachial artery infusions of increasing doses of isoproterenol (0.12, 1.2, 4, 12, and 20 ng/min/100 ml forearm tissue). Measurements were taken following placebo and after one week's treatment with atenolol or bisoprolol under double-blind conditions using a within-patient crossover design. Two patients received 10 mg bisoprolol and 50 mg atenolol daily, and three patients 20 and 100 mg daily, respectively. Both beta-blockers produced a similar fall in blood pressure, heart rate, and plasma renin activity. While CD25 of isoproterenol was comparable for both drugs, forearm blood flow to intra-arterial infusion of isoproterenol increased to a greater extent following bisoprolol (20 mg) than during atenolol (100 mg) treatment. Equieffective cardiac beta-blockade with bisoprolol and atenolol was associated with a lesser degree of vascular beta-adrenoceptor blockade during treatment with the more cardioselective beta-blocker bisoprolol.

Adrenergic beta-Antagonists↗