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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 271 records · Page 15Linked to original sources
PubMed1989

Reciprocal changes in atrial natriuretic factor and aldosterone during angiotensin converting enzyme inhibition in man.

To investigate whether aldosterone responses to angiotensin converting enzyme (ACE) inhibition are affected by changes in atrial natriuretic factor, which is known to inhibit aldosterone secretion, we measured blood pressure, plasma renin activity, aldosterone, atrial natriuretic factor and plasma potassium before and after 1 week of treatment with fosenopril, a long-acting ACE inhibitor, in eight normotensive subjects. Fosenopril caused a slight fall in blood pressure and increased plasma renin activity in all subjects. In contrast, aldosterone and atrial natriuretic factor were, on average, unchanged. However, for both these hormones a wide range of individual responses was observed (aldosterone from -254 to +240 pmol/l, atrial natriuretic factor from +9.7 to -16.6 pmol/l) and a significant inverse correlation was found between the changes in aldosterone and those in atrial natriuretic factor (r = -0.73, P less than 0.05). Plasma potassium was unchanged after the fosenopril treatment. These findings suggest an inter-relationship between atrial natriuretic factor and the aldosterone responses to short-term treatment with an ACE inhibitor.

Adult↗
PubMed1989

Nicorandil, a new vasodilator drug, in patients with essential hypertension.

In 12 mild to moderate hypertensive patients we investigated the acute antihypertensive efficacy of three different doses of nicorandil, a new vasodilating agent which probably acts by increasing the potassium efflux from smooth muscle cells and causing a cellular hyperpolarization. After a 3-day placebo period the patients were given, according to a double-blind Latin-square randomized design, 10, 20 and 30 mg nicorandil as a single acute dose every other day. Blood pressure and the heart rate were measured in both supine and upright positions at various times for 24 h after the dosing; fractional urine collections were obtained at the end of the placebo period and after each active dose. All doses of nicorandil similarly and significantly (P less than 0.01) reduced supine blood pressure, with a peak after 4-6 h (10 mg: -21/-8 mmHg; 20 mg: -20/-9 mmHg; 30 mg: -29/-17 mmHg), and the effect was still present, though reduced, after 24 h; no change in the heart rate was observed. The results from the upright position were similar. There were no significant changes in urine volume and electrolyte excretion during the nicorandil administration. The three different doses of nicorandil caused similar acute blood pressure reductions without change in the heart rate, nor in the urine volume and urinary sodium.

Adult↗
PubMed1989

Antihypertensive efficacy and influence on physical activity of three different treatments in elderly hypertensive patients.

The antihypertensive efficacy and subjective and physical tolerability of three different pharmacological treatments (metoprolol, captopril and the combination of hydrochlorothiazide + amiloride) were compared with placebo in 36 elderly hypertensives (aged 61-79 years), according to a Latin-square double-blind design. The placebo and the active treatments were administered for 2 months. Seated blood pressure was significantly reduced by all the pharmacological treatments compared with placebo, but only metoprolol significantly reduced the heart rate. No haematological or biochemical changes were observed during the study. Physical fitness, evaluated as endurance in a standard cycle ergometer exercise test, was slightly decreased after the treatment with metoprolol and the diuretic combination and slightly improved after treatment with captopril. Subjective tolerability, evaluated by a check-list of symptoms, was better during the active therapies, and in particular during the captopril treatment, than during the placebo treatment. Our results indicate that all three active treatment regimens significantly reduce blood pressure in elderly hypertensives and that captopril appears slightly better tolerated physically and subjectively.

Aged↗
PubMed1989

Angiotensin converting enzyme inhibition and renin release from the kidney.

Experiments were performed in anaesthetized cats, to determine whether renal nerves interfere with the negative feedback action of angiotensin II (Ang II) on renin release. The increase in renin release from the innervated kidney in response to captopril-induced inhibition of Ang II generation was compared with the response of the contralateral denervated kidney. Renin release was measured before (control), and 5, 15 and 30 min after the beginning of captopril infusion (1 mg/kg priming dose followed by 1 mg/kg per h for 30 min intravenously), and 60 min after the end of the infusion. During the captopril treatment renin release from both kidneys increased, but after 15 and 30 min the increase in renin release from the innervated kidneys was significantly larger than that observed in the denervated kidneys. After the captopril infusion was stopped, renin release from both kidneys returned towards control values. These results could not be explained on the basis of the changes in renal haemodynamics, excretory functions and efferent renal nerve activity observed during the captopril infusion. The data suggest that the renal nerves influence the changes in renin release caused by captopril by increasing the sensitivity of juxtaglomerular cells to the negative feedback action of Ang II.

Angiotensin II↗
PubMed1989

Effect of angiotensin converting enzyme inhibition on cardiovascular regulation during reflex sympathetic activation in sodium-replete patients with essential hypertension.

In order to investigate whether angiotensin II (Ang II) may contribute to cardiovascular regulation through facilitation of the adrenergic function, we examined the haemodynamic and humoral effects of the application of lower-body negative pressure (LBNP) in sodium-replete patients with essential hypertension before and after acute and chronic angiotensin converting enzyme (ACE) inhibition. We measured the changes in blood pressure, heart rate, central venous pressure, forearm blood flow, plasma noradrenaline, renin activity and Ang II induced by LBNP of two different magnitudes: a milder one deactivating predominantly the cardiopulmonary receptors (mild LBNP), and a greater one deactivating both the cardiopulmonary and the arterial baroreceptors (strong LBNP). We found that during mild LBNP systemic blood pressure was maintained after acute and chronic ACE inhibition, as in control studies; however, the decrements in forearm blood flow and the increments in forearm vascular resistance caused by LBNP were diminished after ACE inhibition (the latter by 69 and 67%, respectively, in acute and chronic studies), in spite of the fact that the falls in central venous pressure and the increases in noradrenaline (NA) were similar to those observed in control conditions. During strong LBNP, the fall in systemic blood pressure was greater after acute and chronic ACE inhibition than in control conditions and was associated with a reduction in the response of forearm vascular resistance similar to that observed during mild LBNP, while the increments in NA were again superimposable to those seen before ACE inhibition. These alterations in the haemodynamic responses to LBNP induced by ACE inhibition were associated with significant increments in basal plasma renin activity and with marked reductions in Ang II. These findings suggest that even in the sodium-replete state, Ang II exerts a facilitatory action on adrenergic function that is physiologically relevant for the regulation of forearm blood flow and the maintenance of blood pressure during the application of gravitational stresses.

Adult↗
PubMed1989

Value of echocardiographic and ambulatory blood pressure monitoring in hypertension.

This paper reviews the advantages and disadvantages of two new examinations to be employed in hypertension, i.e. echocardiography and ambulatory blood pressure monitoring. It will be emphasized that echocardiography can detect left ventricular hypertrophy in a much more sensitive fashion than electrocardiography thereby allowing a better estimate of the patient's risk of cardiovascular complications. However, this advantage should be considered in the face of the greater cost of this procedure and the inability to obtain reliable echocardiograms in a number of patients. Caution should also be applied in clinical use of ambulatory blood pressure monitoring because of the insufficient data-base on normal ambulatory blood pressure values, the lack of prognostic validation of 24 hour or day-time blood pressure means and the inaccuracy of the automatic blood pressure measuring devices currently available. However, values derived from ambulatory blood pressure monitoring show a better correlation with the target organ damage of hypertension than cuff blood pressure taken in the doctor's office. This justifies the interest in this approach and makes further research on its clinical value worthy.

Adolescent↗
PubMed1989

[Perindopril: first-line treatment of arterial hypertension].

The effectiveness and acceptability of perindopril (P) as an antihypertensive agent were compared with those of captopril (C), atenolol (A) and a combined hydrochlorothiazide + amiloride diuretic (D) in three simultaneous multicentre double-blind trials involving 165, 173 ans 165 patients respectively. After a 1 month placebo period, 3 groups of patients with essential hypertension whose DAP in supine position ranged from 95 to 125 mmHg (means: 103.9, 106.2 and 105.2 mmHg respectively) were allocated at random to treatment with either P (4 mg once a day) or C (25 mg b.d.) or A (50 mg once a day) or D (hydrochlorothiazide 50 mg + amiloride 5 mg once a day) during 3 months. The patients were re-examined monthly and their treatment was modified if their BP was insufficiently controlled (DAP greater than 90 mmHg): first, the dosage of the drug was doubled, then another antihypertensive agent was added, which was either a diuretic (studies with C or A) or a beta-blocker (studies with D). After 3 months, in the monotherapy group BP was controlled in 49 p. 100 of patients on P versus 49 p. 100 on C; 55 p. 100 on P versus 48 p. 100 on A and 72 p. 100 on P versus 72 p. 100 on D. The majority of patients who received P alone were controlled with 4 mg, and only 15 p. 100 required 8 mg. In cases where BP control necessitated a therapeutic combination, the addition of a diuretic was more effective with P than with C (26 p. 100 versus 8 p. 100) or A (23 p. 100 versus 10 p. 100), whereas the addition of a beta-blocker was less effective with P than with D (5 p. 100 versus 13 p. 100). The total percentage of controlled patients was greater with P than with C (75 p. 100 versus 57 p. 100, p = 0.016) or with A (78 p. 100 versus 58 p. 100, p = 0.006); there was non significant difference between P and D (78 p. 100 versus 84 p. 100). The percentages of patients who discontinued treatment were similar with P (6 p. 100 at most), C (4 p. 100), A (5 p. 100) and D (5 p. 100). Most of the side-effects reported with P were minor and unspecific, and their incidence was close to that observed with the other drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

The clinical role of angiotensin converting enzyme inhibitors in antihypertensive therapy in the 1990s.

The traditional stepped-care approach to antihypertensive therapy, which progresses from simple low-dose monotherapy with diuretics and/or beta-blockers to complex combined regimens, is credited with reduction of hypertension-related stroke morbidity and mortality. However, it has achieved little success in reducing hypertension-related coronary morbidity and mortality. Overall mortality of treated hypertensive patients has remained higher than that of the general population, despite decreases in the blood pressure. In the 1990s, hypertension will be viewed as one of several cardiovascular risk factors requiring individualized treatment that takes concomitant diseases into account. Angiotensin converting enzyme (ACE) inhibitors that do not adversely affect serum lipid and glucose levels will play a major role. This class of drugs will also receive attention because of its beneficial action on diabetic nephropathy and its promising cardioprotective effect achieved by improved coronary blood flow, prevention of left ventricular hypertrophy and prevention of certain potentially life-threatening arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Perindopril: first-line treatment for hypertension.

The antihypertensive efficacy and acceptability of perindopril (P) were compared to those of captopril (C), atenolol (A) and a diuretic, hydrochlorothiazide + amiloride (D), in 3 double-blind parallel multicenter studies involving 165, 173, and 165 patients, respectively. Patients with essential hypertension and a supine DBP between 95 and 125 mmHg (mean 103.9, 106.2, and 105.2 mmHg, respectively) after a 1-month placebo period were randomized to P 4 mg once daily (o.d.) and either C 25 mg twice daily, or A 50 mg o.d. or D (hydrochlorothiazide 50 mg + amiloride 5 mg o.d.) and treated for 3 months, with visits at monthly intervals. If necessary, treatment was adjusted at each visit to control BP (supine DBP less than or equal to 90 mm Hg): firstly by doubling the dose and secondly, one month later, by the addition of a second drug, a diuretic in the studies versus C or A, a beta-blocker in the study versus D. At 3 months, BP control on monotherapy in the three studies was achieved in the following proportion of patients: 49% with P vs 49% with C; 55% with P vs 48% with A; 72% with P vs 72% with D. Most of the patients controlled by P received 4 mg, about 15% were controlled with 8 mg. A further percentage of patients was controlled with combination therapy, the combination with a diuretic being more effective with P than with C (26 vs 8%) or A (23 vs 10%) and the combination with a beta-blocker being less effective with P than with D (5 vs 13%). The total percentage of patients controlled was greater with P than with C (75 vs 57%, p = 0.016) or A (78 vs 58%, p = 0.006) and there was no significant difference between P and D (78 vs 84%). The drop-out rate due to side-effects was up to 6% with P, similar to that observed with C (4%), A (5%) and D (5%). Most of the complaints reported with P were minor and non-specific, their incidence being similar to that observed with the other drugs. Cough was reported with both P (1%) and C (2%) as well as with A (1%) and D (1%). Compared to these drugs, the biological acceptability of P was good, no case of renal failure being observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

The risk of hypertension: successes and failures of antihypertensive treatment.

All the antihypertensive trials that have compared active treatment with placebo have given similar and, at the same time, different results. In all trials the therapeutic quotient is above 1, indicating that in all trials mortality and morbidity may be lower (by at least 20%) in the actively treated group. However, the prevented event rate, an absolute measure of benefit, indicates a very large benefit (24 events prevented every 100 patient-years) in the trials involving severe hypertension, and a quite small rate (0.15 event prevented every 100 patient-years) in the MRC mild hypertension trial. Although, taken as a whole, the results of treatment of mild hypertension may appear only moderately encouraging, a considerably greater benefit is observed when a mildly elevated diastolic blood pressure is associated with other risk factors, such as the male sex, cigarette smoking, high blood cholesterol level and elevated systolic blood pressure. Emphasis has been placed, in recent years, upon other limitations in the success of antihypertensive therapy, and it has been stressed that the very effective prevention of cerebrovascular events in the treated hypertensive has not been matched by an equally effective prevention of coronary events. It has also been shown that the risk in treated hypertensives remains higher than that of the general population. Understanding the limitations of current antihypertensive therapy may help in extending treatment successes in the future. A hypothesis that has been recently advanced is that some of the failures of antihypertensive therapy may result from excessive lowering of blood pressure especially in hypertensive patients with ischaemic heart disease (the problem of the 'J'-shaped curve).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1988

Effects of angiotensin and angiotensin blockade on coronary circulation and coronary reserve.

Angiotensin is a potent coronary vasoconstrictor, but little is known of the effects of long-term activation of the renin-angiotensin system on coronary reserve in humans. The effects of exercise on coronary hemodynamics were determined in eight patients with mild essential uncomplicated hypertension, before and after treatment with furosemide (50 mg, to ensure activation of the renin-angiotensin system). Coronary sinus blood flow was measured by thermodilution technique, intra-arterial blood pressure was measured from the ascending aorta, and plasma renin activity was determined by radioimmunoassay. Oxygen supply and demand were derived (using coronary sinus blood flow multiplied by the arteriovenous oxygen difference to equal oxygen supply and heart rate multiplied by the mean systolic blood pressure to equal oxygen demand) both at rest and during isometric exercise (handgrip to 50 percent of maximal effort for three minutes). The study was a single-blind crossover (furosemide versus placebo) design. Furosemide produced a significant reduction in coronary sinus blood flow, associated with an increase in coronary vascular resistance. Changes in mean arterial pressure and heart rate were insignificant. Slight reductions in plasma volume and mean right atrial pressure were observed. During isometric exercise, the increase in oxygen supply for a given increment in oxygen demand was attenuated by furosemide. The contribution of the renin-angiotensin system to this effect was determined by the short-term administration of 25 mg of the angiotensin converting enzyme inhibitor captopril. Forty-five minutes after oral captopril, coronary reserve was restored to pretreatment values. In conclusion, furosemide modulates coronary reserve, and it is likely that this is because furosemide mediates activation of renin-angiotensin system, thus reducing the vasodilatory capacity of the coronary arteries.

Adult↗
PubMed1988

Evaluation of the antihypertensive effect of celiprolol by ambulatory blood pressure monitoring.

The use of ambulatory blood pressure monitoring has gained popularity because it is not subject to those limitations associated with traditional sphygmomanometry (inaccuracy of blood pressure readings, low number of readings, and failure to represent daytime blood pressure readings). In the present study, we provide evidence that the 24-hour mean blood pressure obtained through intraarterial blood pressure measurements in ambulatory patients provides a more accurate diagnosis (and perhaps a prognosis) of hypertension than that provided by cuff-obtained casual blood pressure measurement. Furthermore, despite a reduction in the amount and in the accuracy of the information obtained, blood pressure data provided by noninvasive blood pressure monitoring are also more accurate diagnostically than cuff-obtained casual blood pressure measurements. In 15 essential hypertensive patients in whom celiprolol, 400 mg once daily, was compared with placebo in a randomized double-blind crossover study, the use of noninvasive 24-hour automatic blood pressure monitoring showed that in responsive patients, celiprolol induced a sustained reduction in systolic and diastolic blood pressure throughout the 24 hours. The blood pressure reduction was also apparent during the night, despite the concomitant occurrence of a slight tachycardia. These findings demonstrate that once-daily administration of celiprolol provides an effective lowering of the 24-hour blood pressure profile. This dosing schedule can therefore be regarded as appropriate for antihypertensive therapy.

Adult↗
PubMed1988

Effect on resting blood pressure and blood pressure homeostasis of short-term administration of the alpha 1-adrenergic receptor antagonist, trimazosin, in hypertension.

The effects of trimazosin on blood pressure and cardiovascular homeostasis were studied in 12 subjects with untreated essential hypertension of mild or moderate degree. After a 3-day placebo period, the subjects were given trimazosin at the dose of 50, 100, or 200 mg twice daily (7 am and 7 pm) according to a randomized, double-blind crossover protocol. Each treatment was prolonged for 3 days and separated from the subsequent treatment by a 2-day placebo period. Blood pressure (sphygmomanometry) and heart rate were measured at rest during various laboratory maneuvers on the first and third day of the initial placebo, on the first and third day of the drug periods, and on the second day of the intervening placebo periods. Compared to placebo values, trimazosin caused a reduction in systolic and diastolic blood pressure which was well sustained through the time between the morning and the evening administration of the drug and was accompanied by only a slight tachycardia. the antihypertensive effect was similar in the supine and upright position and in both instances it was greater for the 100 or 200 mg twice daily dose than for the 50-mg twice daily dose. The pressor and tachycardic responses to cold pressor test and to isometric and dynamic exercise were unaffected by the various doses of trimazosin whose antihypertensive effect was therefore similarly evident at rest and during behaviorally occurring blood pressure rises.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Baroreflex sensitivity and its evolution during the first year after myocardial infarction.

Experimental data have indicated that baroreflex sensitivity is often depressed in dogs after myocardial infarction and that this depression correlates strongly with subsequent mortality during episodes of acute myocardial ischemia. This finding has several clinical implications. The present study was undertaken with the objectives of assessing the potential existence of differences in baroreflex sensitivity between men with and without myocardial infarction and the time course during the 1st year after infarction of these potential changes in baroreflex sensitivity. Fifty-three subjects entered the study: 32 postinfarction patients and 21 control subjects. Baroreflex sensitivity was assessed by increasing mean blood pressure by aphenylephrine infusion (70 micrograms/ml) and recording the consequent RR interval changes. Baroreflex sensitivity, expressed as the slope of the regression line relating mean blood pressure to RR interval changes, was evaluated 18 days (n = 32), 3 months (n = 17) and 13 months (n = 10) after infarction. Baroreflex sensitivity was lower in the patients than in the control subjects (8.2 +/- 3.7 versus 12.3 +/- 2.9 ms/mm Hg, p = 0.0001). Moreover, 13 (41%) of 32 patients had a baroreflex slope less than 6.5 ms/mm Hg, which was 2 SD below the mean value of the control subjects. The internal control follow-up study showed that baroreflex sensitivity increased 3 months after infarction to values quite similar to those observed in the control subjects (11.1 +/- 5.3 versus 8.7 +/- 3.5 ms/mm Hg, p = 0.02). No further change was observed between 3 and 13 months after myocardial infarction. These data indicate that baroreflex sensitivity is lower in a proportion of postinfarction patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Dopaminergic control of aldosterone secretion is not mediated by atrial natriuretic factor in patients with essential hypertension.

Both dopamine and atrial natriuretic factor (ANF) are known to suppress aldosterone secretion. Since it is possible that dopaminergic mechanisms facilitate ANF release, we investigated the relationship between these two inhibitory systems by comparing the increases in aldosterone induced by metoclopramide, a dopaminergic antagonist, with decreases in ANF. Aldosterone, ANF, prolactin, plasma renin activity, cortisol and potassium were measured before and after the intravenous injection of 10 mg metoclopramide, blood samples being collected at 15-min intervals up to 2 h after the injection. These studies were performed in patients with essential hypertension who were maintained on a constant sodium intake (100 mmol/day), before and after 5 days of treatment with ibopamine, an orally active dopamine analogue. Before ibopamine metoclopramide induced the expected, marked increases in aldosterone and in prolactin, but only minimal, non-significant decreases in ANF. All other humoral parameters, as well as blood pressure and heart rate, were unaffected by metoclopramide. After ibopamine treatment, which caused a transient natriuretic effect, the responses of aldosterone and of ANF to metoclopramide were similar to those observed in control studies, whereas that of prolactin was enhanced. Thus, it appears that the suppressive effect exerted by the dopaminergic tone on aldosterone secretion is independent of ANF both before and after dopaminergic stimulation.

Aldosterone↗