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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 217 records · Page 12Linked to original sources

Effect of oral dilevalol on forearm circulation in essential hypertension.

In 7 patients with untreated mild essential hypertension, a single 200-mg dilevalol dose was administered orally. Blood pressure (BP, left brachial artery catheter), heart rate (HR), and left and right forearm blood flows were measured and left and right forearm vascular resistances were calculated before and for approximately 3 h after drug administration. Dilevalol administration was followed by a sustained reduction in BP, little change in HR, and a similar pronounced and sustained increase in left and right forearm blood flows and reduction in left and right forearm vascular resistances. At the end of the observation period, the changes in left forearm circulation were unaffected by left brachial artery infusion of saline but markedly reduced by left brachial artery infusion of propranolol at doses that had no effect on BP, HR, and contralateral forearm vasodilatation. Thus, at an oral dose exerting an antihypertensive effect, dilevalol induces a marked and persistent vasodilation due largely to the beta-adrenoceptor agonism of the drug.

Administration, Oral↗

Alpha 1-blocking properties of carvedilol during acute and chronic administration.

Carvedilol is a beta-adrenergic-blocking drug with vasodilating properties. This vasodilation has been ascribed to alpha 1-adrenergic blockade, but it has never been shown in the clinical setting. We addressed this issue by studying eight patients with mild essential hypertension who were given prazosin, 2 mg or carvedilol, 25 mg p.o. following a 2-week washout from previous treatment, according to a randomized double-blind, crossover experimental design. Before and 2 h after the administration of either prazosin or carvedilol, the patients were infused i.v. with increasing doses of phenylephrine (0.2-1.2 microgram/kg/min) and isoproterenol (0.01-0.05 microgram/kg/min). The patients were thereafter maintained on carvedilol 25 mg daily for 3 weeks, and the i.v. phenylephrine and isoproterenol infusions were repeated 2 h after the last tablet administration. The results showed that the single dose of carvedilol and prazosin lowered blood pressure (beat-to-beat finger pressure measurement) to a similar extent, but that heart rate was unaffected by prazosin and reduced by carvedilol. The tachycardic response to isoproterenol was abolished by carvedilol and unaffected by prazosin, whereas the pressor response to phenylephrine was reduced by carvedilol and virtually abolished by prazosin. The antihypertensive, beta-blocking and alpha 1-adrenergic-blocking effects of carvedilol were unchanged following prolonged administration of the drug. Thus, at a clinically effective dose, carvedilol not only has beta- but also sizeable alpha 1-blocking effects. These effects are preserved during prolonged administration of the drug. For a comparable antihypertensive action, however, the alpha 1-blocking effect is less pronounced than that of an alpha 1-blocker such as prazosin.

Adrenergic alpha-Antagonists↗

Echocardiographic and ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension.

High-resolution ultrasonography is a noninvasive technique that allows to investigate the cardiovascular system, in particular the wall thickness and the lumen diameter of the arteries with accuracy and reproducibility. We measured the intima-media thickness of the common carotid artery (CCA) and of its bifurcation (BIF) in 40 patients with essential hypertension, 20 of them with left ventricular hypertrophy (LVH; age 42 +/- 10 years) and 20 without LVH (age 44 +/- 12 years); no other major cardiovascular risk factor was present in all the patients. Both carotid axes have been scanned from different views (anterior, lateral, posterior) on a transversal and longitudinal section using a high-resolution steerable linear array of 5.0 MHz. Carotid diameter and thickness were measured in the longitudinal section. CCA parameters were assessed 20 mm caudally to the flow divider. In patients with LVH, blood pressure (172 +/- 21/108 +/- 9 mm Hg) and left ventricular mass index (156 +/- 38 g/m2) were significantly (p < 0.01) higher than in patients without LVH (blood pressure: 158 +/- 11/99 +/- 12 mm Hg; left ventricular mass index: 98 +/- 10 g/m2), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness of both the CCA and BIF was significantly higher in the hypertensives with LVH (CCA: 0.85 +/- 0.02 vs. 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 vs. 0.70 +/- 0.03 mm, p < 0.01). There was a statistically significant correlation between the carotid wall thickness and the left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prevalence of physiological valvular regurgitation in hypertensive patients: echocardiographic and color Doppler study.

Since the advent of the Doppler color flow echocardiography, the presence of a small degree of insufficiency of the cardiac valves has been detected with relative frequency in structurally and functionally normal hearts. Data about this so-called 'physiological' regurgitation are presently available only in normotensive subjects and athletes. We therefore studied the prevalence of this phenomenon in a group of patients with essential hypertension compared to a population of normotensive subjects. To this purpose, a Doppler color flow echocardiographic study was performed in 130 essential hypertensive patients (72M/58F; age 44.2 +/- 13.5 years; BP 154.3 +/- 12.8/98.3 +/- 7.1 mm Hg) without any evidence of left ventricular hypertrophy or cardiopathy and in 100 normal subjects (59M/41F; age 41.2 +/- 14.8 years; BP 119.1 +/- 8.1/79.2 +/- 8.1 mm Hg). We conclude that in patients with essential hypertension the physiological regurgitant jets are present in one or more cardiac valves; moreover, the regurgitation of the mitral and aortic valve is found with more frequency than in the normotensive control group (36.1 vs. 27.0% and 17.7 vs. 11.0%, respectively). These data suggest that the increased afterload of the left ventricle may play an important role in the pathogenesis of even minor degree of insufficiency of the cardiac valves. As this finding does not appear to have a pathological relevance, the main clinical implication of this study is that it is not advisable to create a jatrogenic heart disease in the hypertensive patients routinely screened by the echo-Doppler technique.

Adolescent↗

ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease.

BACKGROUND: In humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however. METHODS AND RESULTS: In nine normotensive patients with angiographically assessed coronary atherosclerosis, we measured the changes in mean arterial pressure (intra-arterial catheter), heart rate, rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between mean arterial pressure and CBF) induced by the cold pressor test (CPT, 2 minutes) and diving (30 seconds), i.e., two stimuli eliciting a sympathetic coronary vasoconstriction. The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPT caused an increase in mean arterial pressure and heart rate. Despite the increase in RPP (+20.7 +/- 3.2%, p less than 0.01), CBF did not change and CVR increased (+12.2 +/- 4.0%, p less than 0.05). diving caused an increase in mean arterial pressure and a reduction in heart rate. RPP increased (+14.3 +/- 3.5%, p less than 0.01), but despite this increase, there was a reduction in CBF and a marked increase in CVR (+37.3 +/- 7.4%, p less than 0.01). Captopril did not modify the blood pressure and heart rate responses to both stimuli except for a slight accentuation of the bradycardia to diving. Despite the unchanged or only slightly reduced RPP response, the increase in CVR was markedly and significantly attenuated (p less than 0.01). CONCLUSIONS: ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. This is probably due to removal of the facilitating influence of angiotensin II on sympathetic modulation of coronary vasomotor tone.

Angiotensin II↗

Preliminary clinical experience with calcium antagonists in atherosclerosis. Verapamil in Hypertension Atherosclerosis Study Investigators.

Animal experiments have shown that the administration of calcium antagonists can prevent or slow the progression of atherosclerosis by inhibiting calcium overload and interfering with lipid metabolism and deposition. These encouraging results have prompted clinical trials to evaluate the effects of calcium antagonists (dihydropyridines and diphenylalkylamines) on atherosclerotic plaque formation. In patients with coronary heart disease, several studies have already shown that calcium antagonists can have a positive effect on plaque evolution, while in hypertensive patients no such study has been published to date. The Verapamil in Hypertension Atherosclerosis Study is an ongoing multicentre randomised double-blind parallel group trial comparing the antihypertensive efficacy of verapamil SR 240 mg/day with that of chlorthalidone 25 mg/day in 1464 patients with essential hypertension aged 40 to 65 years. In a randomised subgroup of patients (n = 550), who will be followed up for 3 years, B-mode ultrasonography is being employed to evaluate the effects of the 2 drugs on carotid wall thickness and carotid plaque development. Ultrasonographic evaluations are performed at baseline, after 3 months, and 1, 2 and 3 years after a standardised protocol to determine intimal-medial thickness in 4 segments of the extracranial carotid tree. The most interesting result to date is the high incidence of carotid alterations, with plaques present in 35% and arterial wall thickening in 31.8% of the 311 asymptomatic hypertensive patients processed so far. A preliminary evaluation of the antihypertensive efficacy of the trial medications after 6 months of double-blind treatment indicates a 63.5% response rate to monotherapy and a 7.8% drop-out rate because of drug inefficacy or intolerance.

Adult↗

The antiatherogenic effects of antihypertensive drugs: experimental and clinical evidence.

The question whether some classes of antihypertensive drugs have an antiatherogenic action independent of the antihypertensive one has been investigated through a large series of experimental studies; on the other hand, clinical evidence is still rather scanty. Most experimental investigations have shown a significant antiatherogenic action of the antihypertensive compounds, but only when the drug is administered simultaneously with the atherogenic stimulus (mostly cholesterol feeding). When the drug is administered weeks or months after the beginning of atherosclerosis (as in the Watanabe heritable hyperlipemic rabbit), no antiatherogenic effect has been shown, with a single exception. Although the most numerous data available are on calcium antagonists, almost all antihypertensive classes tested have shown some favorable effect on some experimental model. The few clinical studies completed so far as on coronary patients; they have provided arteriographic evidence that various calcium-antagonists have little effect on well-developed lesions and display a beneficial action on new or early lesions only. Ultrasound studies are now underway to compare the effects of calcium-antagonists and diuretics on asymptomatic carotid atherosclerotic lesions in hypertensive patients.

Animals↗

Atherosclerosis and calcium antagonists: the VHAS. The Verapamil-Hypertension Atherosclerosis Study (VHAS) Investigators.

Whether or not some classes of antihypertensive drugs have an anti-atherogenic action independent of the antihypertensive one has been investigated through a large series of experimental studies, primarily involving calcium antagonists. Most experimental investigations have shown a significant anti-atherogenic action of calcium antagonists, but only when the drug is administered simultaneously with the atherogenic stimulus (mainly cholesterol feeding). When the drug is administered weeks or months after the beginning of the atherosclerotic process (as in the Watanabe heritable hyperlipidemic rabbit), with a single exception, no antiatherogenic effect has been shown. The few clinical studies completed so far have been on symptomatic coronary patients. Little is known of the effects of calcium antagonists on asymptomatic lesions in the carotid arteries of hypertensive patients, in whom carotid plaques can be identified and followed-up by non-invasive ultrasound techniques. However, two such trials are underway. The Verapamil in Hypertension Atherosclerosis Study (VHAS) is an ongoing randomized trial, comparing the antihypertensive efficacy of verapamil 240 mg SR with chlorthalidone 25 mg in 1,464 essential hypertensives aged 40-65 years. In a random subgroup of patients (500), who will be followed for three years, B-mode ultrasonography is being carried out blindly to evaluate the effect of the two drugs on carotid wall thickness and on carotid plaques, when present. Preliminary baseline data are available in 440 of the hypertensive patients in whom ultrasound investigation was performed. The mean (+/- SD) age of these patients was 53.7 +/- 6.9 years; 32.5% had echocardiographically normal carotid walls; 30.9% showed intima-media thickening; and 36.6% had one or more plaques.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Has antihypertensive treatment prevented vascular disease or vascular events?

Our current knowledge of the effects of antihypertensive therapy is based on a large number of therapeutic trials based on mortal and morbid cardiovascular events. Although these events are indeed "hard" data, extrapolations from the results of trials based on events cannot be applied to possible effects on the underlying cardiovascular disease, particularly coronary artery disease, as the mechanisms responsible for the precipitation of events are often different from the mechanisms leading to disease. Once a distinction between prevention of disease and prevention of events is made, then both must be considered to be different, but essential, goals of antihypertensive therapy. The prevention of events is a short-term goal for patients who already have disease, and can be easily appreciated by traditional event-based trials; the prevention of disease, however, is a long-term goal that can be appreciated clinically only after years of treatment, but can be assessed within a shorter time frame by measuring plaque development, as in new types of randomized trials. Studies of the potential actions of antihypertensive drugs on the mechanisms precipitating events, particularly thrombotic factors, may further supplement our current knowledge in our search for the most appropriate treatment of the hypertensive patient.

Antihypertensive Agents↗

Acute effects of cilazapril on coronary hemodynamics in patients with renovascular hypertension.

The effects of converting enzyme inhibition on coronary and systemic hemodynamics in the presence of a chronically activated renin-angiotensin system were investigated in five renovascular hypertensive patients with no ECG/echocardiographic evidence of left ventricular hypertrophy. Coronary blood flow (CBF, thermodilution technique), intra-arterial blood pressure, AVO2 difference (coronary sinus), heart rate, and coronary vascular resistance were measured at rest, during isometric exercise (handgrip to 50% of maximal effort for 3 min) before and 60 min after 2.5 mg of oral cilazapril. The drug induced a prompt, significant decrease in mean arterial pressure and a sustained increase in CBF. The performance of handgrip after cilazapril resulted in higher increases in CBF for a given increase in myocardial oxygen requirements. These observations suggest that angiotensin II (Ang II) maintains the ability to alter the control mechanisms of CBF even under long-term conditions and that converting enzyme inhibition reverses the Ang II-induced effects on coronary hemodynamics.

Adult↗

Regulation of vasopressin release in moderately severe essential hypertension.

Vasopressin plasma concentrations have been measured in two groups of subjects, 13 moderate essential hypertensive patients without target organ damage and eight control normotensive subjects, before and after the assumption of the upright position, and intravenous infusions of hypotonic saline (0.45% NaCl, 0.25 ml kg-1 min-1 for 1 h) and hypertonic saline (100 mmol NaCl in 50 ml). Plasma vasopressin in recumbent baseline conditions was not significantly different in the two groups. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels, which were not significantly different between the two groups. Plasma renin activity increased in the upright position, was reduced by administration of hypotonic saline and unaffected by hypertonic saline, with no differences between the hypertensives and normotensives. After hypertonic saline, urinary flow rate and urinary sodium excretion in the hypertensive group increased to values significantly (p less than 0.05) higher than in normotensive subjects. In conclusion our study excludes significant alteration of vasopressin regulation in moderate uncomplicated hypertension. In hypertensives although the response of vasopressin to an osmotic load is preserved, the data suggest that the renal handling of the osmotic load may be altered.

Adult↗

Treatment of hypertension in the elderly: effects on blood pressure, heart rate, and physical fitness.

The subjects were 36 hypertensive patients aged 61 to 79 years (mean, 66 years). After a placebo run-in period of one month, each patient was randomly assigned to two months of treatment with 100 mg of metoprolol, 50 mg of captopril, or 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride daily, or placebo. The doses were doubled if diastolic pressure was above 95 mm Hg after one month of treatment. Blood pressure, heart rate, and physical fitness (endurance during a standard cycle ergometer exercise) were measured and side effects assessed after each two-month treatment period. Mean blood pressures were significantly lower after treatment with metoprolol (154/92 mm Hg), captopril (157/92 mm Hg), and hydrochlorothiazide-amiloride (152/91 mm Hg) than after placebo (170/101 mm Hg). Heart rate was significantly lower after treatment with metoprolol (64 beats/minute) than after placebo (77 beats/minute). Exercise endurance was lower after treatment with metoprolol (498 seconds) and hydrochlorothiazide-amiloride (519 seconds) than after placebo (529 seconds) and higher after captopril (541 seconds). More patients reached the target exercise work load after captopril than after the other treatments. No patients withdrew from treatment because of side effects or abnormal laboratory test results. All three active treatments benefited the elderly hypertensive patients and did not lower their physical fitness. Captopril appeared to be more effective than the other two treatments.

Aged↗

Use of intravenous digital subtraction ventriculography in the evaluation of left ventricle volumes and ejection fraction.

Although intravenous digital subtraction ventriculography (IDSV) is increasingly used to estimate end-diastolic left ventricular volume (EDV), end-systolic left ventricular volume (ESV) and left ventricular ejection fraction (EF), its ability to reproduce the precise estimates provided by left ventricle cineangiography (LVCA) and its role in clinical cardiology have not been unequivocally established. In 32 patients subjected to cardiac catheterization for a variety of cardiac disorders and a normal or reduced left ventricular function the EDV, ESV and EF provided by a 30 degrees right anterior oblique LVCA were compared with those provided by a 30 degrees right anterior oblique IDSV. The mean EDV, ESV and EF obtained by IDSV in the 32 patients were superimposable on those obtained by LVCA. The individual EDV, ESV and EF values provided by the two methods were all related in a close linear fashion. For EF the correlation coefficient was 0.98 and the 90% confidence interval of the mean difference between the two series of values was +/- 6.1%, i.e. +/- 10% error compared to the mean EF provided by LVCA. Thus IDSV is a reliable and not too invasive method for estimating left ventricle volumes and ejection fraction. It might provide serial estimations with a better assessment of the evolution of a patient's disease and the effect of treatment.

Adult↗

Effects of long-term blood pressure control on left and right ventricular structure and function in hypertensive patients.

The functional and anatomical abnormalities of the right ventricle may occur in hypertensive patients with left ventricular hypertrophy (LVH). The present study was designed to assess the functional and structural changes in both left and right ventricles induced by chronic antihypertensive therapy. Doppler and standard echocardiography were performed in 10 hypertensive patients with LVH before and after 1 year of treatment with captopril alone (5 patients) or captopril plus nifedipine (5 patients). We found that the left ventricular mass index and right ventricular thickness were significantly reduced in all patients when compared with pretreatment values. Furthermore, the Doppler-derived diastolic filling indexes show a significant improvement of both ventricular chambers. Our data suggest that anatomical and functional changes induced by therapy in hypertensive patients are not limited to the left ventricle but also involve the right ventricle.

Blood Pressure↗

Left ventricular diastolic function in athletes and borderline hypertensives with mild cardiac hypertrophy.

The aim of this study was to evaluate the diastolic function in athletes and in young borderline hypertensives with mild left ventricular hypertrophy. Left ventricular filling was assessed by echo Doppler measurement of transmitral flow velocity in 18 soccer players (age 22 +/- 4 years, left ventricular mass index, LVMI 136 +/- 12 g/m2), in 15 borderline hypertensives (age 21 +/- 3 years, LVMI 137 +/- 9 g/m2), and 20 normotensive subjects (age 22 +/- 4 years, LVMI 93 +/- 10 g/m2) as reference group. We found that left ventricular filling profile was similar in borderline hypertensives, in athletes and in normotensive subjects. These findings suggest that, at least in the early stage, mild cardiac hypertrophy secondary to borderline blood pressure elevation is characterized by indexes of diastolic function not different from those found in athletes with physiological hypertrophy.

Adult↗

Cardiac structure and function before and after acute and chronic verapamil administration in hypertensive patients.

The aim of this study has been to analyze the acute and chronic effects of oral verapamil on diastolic function indices, derived from Doppler echocardiography, and left-ventricular (LV) dimensions and mass, assessed by M-mode echocardiography, in hypertensive patients without LV hypertrophy. 12 patients with essential hypertension were studied in basal conditions and (1) after a single oral administration of verapamil 160 mg and placebo in a double-blind protocol and (2) over chronic treatment (12 months) with verapamil 240 mg/day. At baseline, the ratio between early and atrial-induced transmitral velocities (E/A ratio) was lower in patients than in 12 age-matched normal subjects (1.08 +/- 0.2 vs. 1.51 +/- 0.3, p less than 0.01). Acute verapamil administration significantly decreased arterial blood pressure (162 +/- 26/101 +/- 8 to 142 +/- 12/88 +/- 7 mm Hg, p less than 0.01 after 2 h) and increased the E/A ratio to 1.26 +/- 0.3 (p less than 0.05) after 3 h. No change in ventricular dimensions and heart rate was observed. After chronic therapy, we found a further increase in the E/A ratio in 10 responder patients (1.49 +/- 0.3, p less than 0.01). The LV mass index, that was higher than in normal subjects before the treatment (118 +/- 16 vs. 91 +/- 11 g/m2, p less than 0.01), was significantly reduced (100 +/- 17 g/m2, p less than 0.05 vs. basal, nonsignificant vs. normal subjects). Our results demonstrate that acute administration of verapamil only partially improves the abnormal indices of diastolic function in hypertensive patients, whereas chronic treatment, by reducing LV mass indices and blood pressure to normal values, can completely normalize the indices of LV diastolic filling.

Adult↗