Search PubMed⌕ Search

Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 289 records · Page 16Linked to original sources
PubMed1988

Antihypertensive efficacy of nicardipine-based treatment in patients of different age and in patients with isolated systolic hypertension.

The relationship between age and the antihypertensive efficacy of calcium antagonists has been investigated by different authors with conflicting results. In order to evaluate this relationship an Italian multicentre study investigated 2184 patients with mild to moderate hypertension with an age range of 24-90 years. Initial treatment consisted of nicardipine monotherapy (daily dose 40-80 mg/day in two or three oral administrations); after 4 weeks other antihypertensive agents could be added in non-responders (seated blood pressure greater than 160/95 mmHg). The patients were divided into four groups according to age (less than or equal to 55 years, 56-65 years, 66-75 years and greater than 75 years). Nicardipine-based treatment reduced systolic and diastolic blood pressures to similar levels independently of the age of the patients. The correlation between systolic blood pressure reduction and age was only 0.141 (NS). The percentage of patients treated with nicardipine monotherapy was similar in all age groups, but the incidence of side effects, mostly transient and mild, was lower in older than in younger patients. In patients older than 65 years with isolated systolic hypertension (systolic pressure greater than 160 and diastolic pressure less than 90 mmHg), nicardipine-based therapy significantly lowered systolic blood pressure only from 180 +/- 11/87 +/- 6 to 148 +/- 14/84 +/- 8 mmHg.

Age Factors↗
PubMed1988

Nifedipine does not blunt the aldosterone and cardiovascular response to angiotensin II and potassium infusion in hypertensive patients.

The antihypertensive response of calcium antagonists of the dihydropyridine series, although accompanied by a significant increase in plasma renin activity (PRA), is generally not associated with a comparably significant rise in plasma aldosterone (PA). This has been suggested to be due to the adrenal glomerular cell responsiveness being dependent on calcium entry. To investigate this hypothesis, angiotensin II (AII; 0.15, 0.375, and 0.750 micrograms/min, each step for 20 min) and KCl (30 mmol/50 min) were infused on separate days in 11 hypertensive patients kept at a constant daily intake of 100 mmol sodium and 40 mmol potassium, before and after 1 week of nifedipine treatment (20 mg b.i.d.). Supine blood pressure (BP) was significantly (p less than 0.01-p less than 0.001) reduced after nifedipine treatment; supine PRA increased significantly (p less than 0.01), while PA did not change significantly. No change in plasma potassium level was seen during nifedipine treatment. The dose-dependent mean BP rises induced by AII were slightly blunted during nifedipine treatment, whereas the PRA decreases and the PA rises after the peak infusion were not significantly different before and during nifedipine administration. Potassium infusion had no significant effect on BP, and caused a significant and similar rise in PA before and during nifedipine administration, while PRA decrease was more pronounced after nifedipine treatment. As previously shown in normotensive subjects, and also in hypertensive patients, aldosterone responses to two major stimulants, such as AII and potassium, do not appear to be blunted by treatment with a calcium antagonist.

Adult↗
PubMed1988

Nitrendipine and ACE inhibitors.

There is evidence from several studies of the clinical usefulness of an antihypertensive regimen combining a calcium antagonist and an angiotensin converting enzyme (ACE) inhibitor. The mechanisms of this mutual potentiation between agents of these two classes are probably numerous. First, dihydropyridines cause a variable amount of reflex sympathetic activation, whereas ACE inhibitors blunt sympathetic activity at different central and peripheral levels. Second, dihydropyridines produce an almost exclusive arteriolar dilatation, and a more balanced arteriolar and venous dilatation might result from their association with an ACE inhibitor. Finally, stimulation of renin release and the consequent generation of angiotensin II are facilitated by dihydropyridines, and this increased generation of angiotensin II can be blocked by ACE inhibition. More limited information is available on the doses of calcium antagonist and ACE inhibitor that are best suited for combined therapy. Careful studies should be performed to compare the dose-response curves of either agent to be combined and of possible dose combinations, particularly if combinations of agents of the two classes are planned in the same tablet.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intra-arterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats in which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+PI/+SBP) or fell (-PI/-SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and -PI/-SBP sequences of 3 beats were found whereas the number of sequences of 4, 5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of +PI/+SBP (7.6 +/- 2.0 msec/mm Hg) and -PI/-SBP (6.4 +/- 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 +/- 4.7 and 62.6 +/- 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (-33.2% for +PI/+SBP and -31.7% for -PI/-SBP) and less steep in hypertensive subjects (-40.3 and -36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations in sensitivity due in part to hemodynamic, temporal, and behavioral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Neural control of circulation before and after intravenous urapidil in essential hypertension.

Drugs interfering with sympathetic influences on the cardiovascular system have been shown to effectively lower blood pressure in hypertension. However, sympathetic cardiovascular control is involved in blood pressure homeostasis, which means that these drugs may produce potential adverse haemodynamic effects that may reduce the benefit of their antihypertensive action. This paper summarises the results of a study in which we examined the effects of urapidil on the arterial baroreflex and the cardiopulmonary reflex in 6 essential hypertensive patients given 25 mg of the drug intravenously. The dose of the drug used caused a marked reduction in arterial blood pressure (direct measurement). However, pressor and depressor responses to carotid baroreceptor deactivation and stimulation (neck chamber device), respectively, were not modified when compared with those observed in the placebo period. This was also the case for increases and reductions in both forearm vascular resistance and plasma noradrenaline (norepinephrine) concentrations induced by deactivating and stimulating cardiopulmonary receptors, respectively. The pressor and tachycardic responses to handgrip and cold exposure were also unaffected by the drug. It is concluded that when administered at a clinically effective dose urapidil does not adversely affect major reflex mechanisms involved in neural cardiovascular regulation. This has favourable implications for the use of the drug in clinical practice.

Antihypertensive Agents↗
PubMed1988

Systemic haemodynamic and humoral changes during urapidil treatment in hypertensive patients.

Urapidil, a new antihypertensive agent exerting a peripheral alpha 1-postsynaptic blocking action and an additional action at the central level, has some characteristics which may correct the underlying pathophysiological abnormalities found in the great majority of hypertensive patients. When administered acutely and chronically, urapidil significantly lowers blood pressure in hypertensive patients by reducing total peripheral resistance, while cardiac output is unchanged or only slightly elevated. The blood pressure reduction can cause a decrease in cardiac mass in patients with left ventricular hypertrophy. Urapidil has been successfully administered also in patients with congestive heart failure and in hypertensive crises during or following surgical procedures; in all these conditions urapidil lowers total peripheral resistance, but blood pressure is lowered only in patients with hypertensive crises and no clinically relevant reduction in blood pressure is found in patients with congestive heart failure. The acute administration of urapidil has shown a trend towards a rise in plasma renin activity, in plasma aldosterone and in plasma catecholamines; on the whole, however, the activation of these systems has been mild.

Adrenergic alpha-Antagonists↗
PubMed1988

Reflex control of circulation and angiotensin converting enzyme inhibition in man.

Removal of the facilitating effect of angiotensin II on sympathetic cardiovascular influences may enhance the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors but may also disturb reflexes involved in blood pressure homeostasis. To test this hypothesis in essential hypertensive subjects, the forearm vasomotor response to cardiopulmonary receptor deactivation (lower body negative pressure) was studied before and after acute or prolonged administration of captopril at doses capable of lowering blood pressure and blocking the formation of angiotensin II. After either acute or prolonged captopril administration there was less response (i.e. forearm vasoconstriction) than in the no-drug state. However, in the same subjects, another reflex response to cardiopulmonary receptor deactivation, the increase in plasma renin activity, was not blunted by the drug. Furthermore, the other major reflex responsible for blood pressure homeostasis, the arterial baroreflex, was left unchanged or was even favoured by administration of clinically effective doses of captopril. This finding applied to both the heart rate and the blood pressure modulating ability of the reflex (vasoactive drug and neck chamber techniques, respectively). Thus, reflex control of circulation may be adversely affected by ACE inhibition. However, this does not include all reflex targets and at least one major reflex is preserved following this pharmacological intervention. This may explain why our patients showed no orthostatic hypotension during chronic treatment with ACE inhibitors.

Blood Pressure↗
PubMed1987

Role of calcium antagonists in systemic hypertension.

Despite the physiologic rationale of their use in hypertension, traditional vasodilators such as hydralazine and minoxidil are often relegated to the second and, more often, to the third and fourth steps of step-care programs. Although they are powerful blood pressure-lowering agents, they cause tachycardia, excessive renin stimulation and sodium retention, and cannot be used as the only antihypertensive agent. The characteristics of the antihypertensive action of calcium antagonists make them suitable for monotherapy. Indeed, all calcium antagonists, while effectively lowering blood pressure through vasodilation, either do not affect heart rate (verapamil and its analogs) or cause a moderate and transient heart rate increase (dihydropyridine compounds). Dihydropyridines also possess a natriuretic effect, probably due to inhibition of tubular sodium transport. The natriuretic effect is evident during the first 2 days of administration, but a small negative sodium balance persists for at least 1 week. There is no increase in body weight or fluid volumes with long-term administration of calcium antagonists with a marked acute natriuretic response, such as dihydropyridines, and those antagonists with a very moderate immediate natriuretic response, such as verapamil. All calcium antagonists, therefore, appear capable of preventing the sodium and water retention that vasodilatation would otherwise entail. More liberal step-care guidelines are now possible to find the agent most suitable for the individual patient. In these guidelines, calcium antagonists, as well as angiotensin converting enzyme inhibitors, are considered as possible first-choice agents along with diuretics and beta blockers.

Adrenergic beta-Antagonists↗
PubMed1987

Human renovascular effects of dopexamine hydrochloride: a novel agonist of peripheral dopamine and beta 2-adreno-receptors.

The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity. Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B) = 504 ml X min-1; after treatment (D) = 605 ml X min-1), CO (B = 5.9 l X min-1; D = 6.7 l X min-1), heart rate (B = 77 beats/min; D = 100 beats/min) and systolic blood pressure (B = 143 mmHg; D = 166 mmHg) were observed on administration of dopexamine 3 micrograms X kg-1 X min-1, with insignificant changes in diastolic blood pressure (B = 84.4 mmHg; D = 90 mmHg) and total peripheral resistance (B = 17.85; D = 17.25 Units). There was a slight but significant reduction in renal vascular resistance (B = 20.59, D = 18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B = 8.5%, D = 9%), consistent with selective renal vasodilatation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA1-receptor mediated effect.

Adrenergic beta-Agonists↗
PubMed1987

Sympatho-renal interactions.

The renal nerves appear to be involved in the control of cardiovascular homeostasis and volume balance both in physiological and in pathological conditions such as experimental hypertension. Anatomical and electrophysiological evidence suggests that the kidney has a diffuse sensory innervation connected with areas in the brain and spinal cord that are known to regulate cardiovascular functions by both neural and humoral mechanisms. The demonstration of the existence of neural reno-renal reflexes controlling several renal functions indicates that a functional balance between the two kidneys exists and may play an important role in the moment-to-moment control of kidney functions.

Animals↗
PubMed1987

Effects of a low-sodium diet on antihypertensive and natriuretic responses to acute administration of nifedipine.

This study was designed to determine (1) whether different sodium intakes influence the acute antihypertensive effect of a single dose of nifedipine, (2) whether the combination of nifedipine and a low-sodium diet lowers blood pressure to a greater extent than administration of nifedipine alone and (3) whether a reduction in sodium intake can dissociate the antihypertensive from the natriuretic response to nifedipine. We studied 11 hypertensive patients in order to investigate the antihypertensive and natriuretic effects of a single oral dose of 10 mg nifedipine during sodium repletion (100 mmol/day sodium intake) and depletion (20 mmol/day sodium intake), with a constant potassium intake (40 mmol/day). Nifedipine significantly (P less than 0.01) lowered supine blood pressure, from 178 +/- 14/107 +/- 7 to 161 +/- 12/100 +/- 7 mmHg during sodium repletion and from 152 +/- 12/95 +/- 9 to 142 +/- 11/90 +/- 8 mmHg with sodium depletion. The natriuretic and diuretic actions of nifedipine were marked and statistically significant during sodium repletion and almost absent during sodium depletion. We conclude that (1) the acute antihypertensive effect of a single dose of nifedipine is present both in the sodium-replete and in the sodium-depleted states, although during sodium depletion the nifedipine effect is somewhat reduced in extent and duration; (2) the blood pressure reached after administration of nifedipine in the sodium-depleted state is significantly lower than the values reached after nifedipine treatment in the sodium-replete state; (3) the natriuretic action of calcium antagonists is not essential to the acute antihypertensive action of these compounds.

Adult↗
PubMed1987

Calcium antagonists and responsiveness of the adrenal glands to aldosterone-releasing stimuli in hypertensive patients.

This study was designed to determine whether a reduced responsiveness of adrenal zona glomerulosa to physiological stimuli could be responsible for the lack of a proportional rise in plasma renin activity and plasma aldosterone during administration of calcium antagonists. We selected 11 hypertensive patients and measured the rise in plasma aldosterone in response to infusions of angiotensin II or potassium chloride before and after a 7-day treatment with fully antihypertensive doses of nifedipine (20 mg twice a day), while the patients were kept on a constant daily intake of sodium (100 mmol) and potassium (40 mmol). The treatment with nifedipine induced a significant reduction in both systolic and diastolic blood pressures; the infusions of angiotensin II (0.150, 0.375 and 0.750 microgram/min, each rate for 30 min) and of potassium chloride (50 mmol in 500 ml of 5% glucose in 50 min) caused similar rises in plasma aldosterone before and during the administration of the calcium antagonist. Therefore, our results indicate that responsiveness of the adrenal zona glomerulosa to physiological stimuli is maintained despite blockade of calcium channels capable of significantly lowering arterial blood pressure.

Adrenal Glands↗
PubMed1987

Angiotensin-converting enzyme inhibitors in essential hypertension.

At the Cambridge Conference, the pros and cons of various classes of antihypertensive drugs were extensively discussed, including the place of angiotensin-converting enzyme inhibitors in today's spectrum. A consensus was easily reached that the most important advantage of having the present broad armamentarium of antihypertensive drugs is that a wide choice is now available from which to find the most suitable agent for the individual patient. A revised stepped-care design was proposed, in which the doctor has the choice of starting antihypertensive therapy with a thiazide diuretic, a beta-blocker, an angiotensin-converting enzyme inhibitor, or a calcium antagonist. Small doses of any agent should be used to start with, and doses should not subsequently be increased beyond that at which side effects appear. Should such symptoms occur, the doctor has the choice of either switching to another first-step compound or reducing the dose of the first agent and combining it with one of other available drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Effects of angiotensin II blockade on the responses of the pituitary-adrenal axis to corticotropin-releasing factor in humans.

We investigated the possibility that angiotensin II (ANGII) augments the sensitivity of the pituitary to corticotropin releasing factor (CRF) by comparing, in patients with essential hypertension, the responses of plasma adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and renin activity to a bolus injection of either 0.5 or 1.0 microgram/kg of synthetic ovine CRF in control conditions and after chronic treatment with the converting enzyme inhibitor captopril to block the formation of ANGII; the effects of CRF were examined up to 4 h after its administration. In control studies, we found that the two doses of CRF induced similar increments in ACTH and cortisol, the levels of which remained elevated throughout the studies; these changes were associated with increments in plasma aldosterone that were dose dependent, less pronounced, and of shorter duration and with a slight decrease in plasma renin activity. Captopril treatment increased basal plasma renin activity and lowered plasma aldosterone while leaving basal ACTH and cortisol unchanged. During converting enzyme inhibition, the responses of ACTH and cortisol to CRF were similar to those observed in control studies, whereas the changes in plasma aldosterone and plasma renin activity were, respectively, smaller and greater. From these results, it appears that during ANGII blockade the sensitivity of ACTH to CRF stimulation is unaffected, whereas that of the adrenals to ACTH is selectively reduced at the level of the zona glomerulosa.

Angiotensin II↗