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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 361 records · Page 20Linked to original sources
PubMed1985

Does beta 1-selective agonistic activity interfere with the antihypertensive efficacy of beta 1-selective blocking agents?

In order to investigate whether addition of beta 1-selective agonism can interfere with the antihypertensive efficacy of beta 1-selective adrenoceptor blockers, two separate studies were carried out to evaluate the effects on blood pressure and heart rate of three beta 1-selective blockers with or without varying degree of beta 1-selective agonism. In hypertensive patients at rest, the greatest blood pressure reduction and bradycardia were found with atenolol, a beta 1-selective blocker without any agonistic activity; a consistently smaller effect on blood pressure and heart rate was observed with Visacor (ICI 141 292), a beta 1-selective blocker with moderate beta 1-selective agonism, whereas no clinically relevant decrease in blood pressure occurred with Corwin (ICI 118 587), the beta 1-selective blocker with high beta 1-selective agonism. In contrast, during exercise-induced sympathetic activation, all three compounds reduced systolic blood pressure and heart rate to a similar degree.

Adrenergic beta-Agonists↗
PubMed1985

The responses of adrenocorticotrophic hormone and cortisol to insulin-induced hypoglycaemic stress in man are unimpaired during chronic converting enzyme inhibition.

In vitro and animal studies indicate that circulating angiotensin II (ANG II) can stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion, but it is far from established that ANG II has a physiologically relevant influence on steroidogenesis. We studied the effects of hypoglycaemia induced with insulin injection (0.15 IU/kg) in patients with essential hypertension to answer this question. Hypoglycaemia was induced before and after a short term course of treatment with the converting enzyme inhibitor captopril to obtain a sustained blockade of ANG II formation. Alterations in serum glucose, plasma potassium, plasma ACTH, cortisol, renin activity and aldosterone were examined. In control studies there was a profound fall in serum glucose and plasma potassium after insulin, associated with increments in plasma renin activity, which correlated with those of aldosterone but not with those of ACTH and cortisol. Chronic captopril increased baseline plasma renin activity and lowered baseline aldosterone while leaving ACTH and cortisol unchanged. During converting enzyme inhibition the insulin-induced decrements in glucose and potassium, as well as the increments in ACTH, cortisol and aldosterone, were similar to those observed in control studies, whereas the increments in plasma renin activity were much greater. From these results it does not appear that ANG II has a relevant influence on ACTH and cortisol production, or on their responses to hypoglycaemic stress. Rather, these findings indicate that even under the present experimental conditions ANG II is the primary regulator of aldosterone secretion. However, this function can be taken over by ACTH when the generation of ANG II is blocked.

Adrenocorticotropic Hormone↗
PubMed1985

Prospectives for angiotensin converting enzyme inhibition in heart diseases.

Angiotensin converting enzyme (ACE) inhibitors are not known to have a direct effect on the myocardium. However, there is some evidence to suggest that they can play an important role in protecting the heart during the evolution of hypertensive and coronary arterial disease, both acutely and on a long term basis. Reduction of afterload by balanced arterial and venular dilatation has led to a sustained improvement of cardiac performance both in hypertension and heart failure. Reversal of cardiac hypertrophy has been shown to restore inotropic responsiveness to stimulators of the adenylate cyclase system. Following myocardial infarction, captopril has prevented undue ventricular dilatation and normalized left ventricular chamber stiffness; this prevented deterioration of cardiac function and improved long term survival after infarction. Control of secondary aldosteronism and prevention of hypokalaemia can play an important role in the prevention of cardiac arrhythmias. The lack of reflex sympathetic stimulation during long term captopril therapy can also play a favourable role in that respect. Although highly speculative, evidence is accumulating that ACE inhibition could have a cardioprotective effect in acute myocardial ischaemia. It is based on the demonstration that renin can be produced by myocardial cells, that angiotensin is liberated by the ischemic myocardium and that angiotensin in high renin conditions plays an active constrictor role in regulating the coronary circulation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Interactions between the sympathetic nervous system and the kidney: experimental observations.

Increasing evidence suggests that the renal nerves may contribute to the pathogenesis of several types of experimental hypertension. It has been demonstrated that renal denervation can either attenuate the severity or delay the development of hypertension in spontaneously hypertensive rats (SHR), in DOCA-salt treated rats and in renovascular hypertensive rats. On the other hand, intrarenal administration of catecholamines has been shown to elicit an increase in systemic arterial pressure as long as the infusion is continued. The underlying mechanisms by which renal nerves might participate in the regulation of cardiovascular homeostasis have not been entirely clarified. It is known that efferent renal nerve activity, by exerting a direct influence on renal arteriolar tone, renin release and sodium and water excretion, can interfere with the control of arterial pressure by modifying peripheral resistances, circulating angiotensin II and volume balance. In addition, a role of afferent renal nerve activity in cardiovascular control and, possibly, in the pathogenesis of renovascular hypertension, has recently been proposed after the demonstration of mechano- and chemoreceptors inside the kidney. Indeed, blood pressure is reflexly influenced either by several manoeuvres applied to the kidney or by the electrical stimulation of afferent renal nerve fibres. Afferent and efferent renal nerve activity appear to be closely related since recent experiments by our group have provided further evidence of the existence of neural renorenal reflexes by which one kidney exerts a tonic inhibitory effect on the release of renin from juxtaglomerular cells and on tubular sodium and water reabsorption of the contralateral kidney.

Afferent Pathways↗
PubMed1984

Treatment goals in hypertension.

Since the realization that hypertension was a risk factor for cardiovascular disease, methods of lowering elevated blood pressure have been developed. The main goal of antihypertensive treatment is to prevent or to arrest cardiovascular damage. Based on the successes and failures encountered for over 30 years or more of therapeutic experience in hypertension, several treatment goals have been established. Previously, it was claimed that the advantages of lowering blood pressure were not dependent on the antihypertensive drug used. Now, this is being questioned. For instance, fatigue is often observed in hypertensive patients treated with drugs that reduce cardiac output and limit peripheral blood flow. Is it therefore more rational to reduce blood pressure by returning increased vascular resistance to normal? Since antihypertensive therapy is life-long, we are becoming increasingly aware of the long-term effects (both beneficial and adverse) of antihypertensive drugs. The metabolic changes caused by current antihypertensive drugs are now being studied in detail. The potassium-depleting action of diuretics is well-known, and the significance of such an effect is being re-examined. The effects of various antihypertensive agents on serum lipids are relatively recent observations, the clinical importance of which is worthy of wider discussion and investigation. The abolition or reduction of all vascular complications of hypertension is the goal for which current antihypertensive treatment has most often failed. Whereas prevention of cerebrovascular accidents, renal failure, and heart failure has indeed been successfully achieved, coronary complications (the most frequent adjunct of hypertension) have been little influenced by antihypertensive therapy. Is this because coronary heart disease may be simply an associated disease, rather than a consequence of hypertension? Or is this because the beneficial action of the most widely used antihypertensive drugs on vascular disease is largely counteracted by unfavorable metabolic effects? These and similar questions have to be debated and resolved before we can define treatment goals more precisely and develop the most appropriate means to achieve them.

Antihypertensive Agents↗
PubMed1984

Twenty-four-hour blood pressure profile and blood pressure variability in untreated hypertension and during antihypertensive treatment by once-a-day nadolol.

First, blood pressure and heart rate variability was studied in 89 normotensive and hypertensive ambulatory subjects with the use of an intra-arterial monitoring device. Short- and long-term variabilities were analyzed by computer. Absolute variabilities (standard deviations) were greatest in patients with hypertension, but relative variabilities (variation coefficients, i.e., standard deviations as percent of means) were slightly lower in the subjects with more severe hypertension. Second, the effect of nadolol on 24-hour blood pressure and heart rate values and on their variability was assessed in seven ambulatory patients with essential hypertension by means of the same intra-arterial device and computer analysis. Two recording sessions were performed (1) without treatment and (2) after 10 days' administration of nadolol once a day (dose range, 80 to 320 mg). Nadolol, given once a day, was shown to reduce blood pressure uniformly throughout the 24-hour period without loss of activity in the hours farthest from administration. The lack of alteration in relative blood pressure variability suggests that nadolol lowers blood pressure without interfering with the mechanisms involved in cardiovascular homeostasis. Reduction in heart rate variability after nadolol suggests less chance of tachycardia episodes in patients with angina and/or arrhythmias receiving nadolol.

Adrenergic beta-Antagonists↗
PubMed1984

Arterial baroreceptor control of blood pressure in man.

Information on arterial baroreceptor control of circulation is much more restricted in man than in animals, largely because of the limitations in the techniques available in humans for this type of study. However, recent utilization of the neck chamber technique that addresses the primary function of an arterial baroreflex, i.e. blood pressure control, has provided a significant amount of information. This paper describes baroreceptor control of blood pressure as derived from neck chamber studies in normal people and discusses its modifications by exercise and ageing, and its participation in a phenomenon such as spontaneous blood pressure variability. The description given here is focused on aspects of this baroreceptor control that have changed the concept of the overall arterial baroreceptor function developed by means of techniques for studying only baroreceptor influences on heart rate.

Adult↗
PubMed1984

Verapamil and propranolol: a comparison of two antihypertensive agents.

Verapamil, a calcium antagonist, was compared with propranolol, a widely used beta-adrenoreceptor blocker, in hypertensive patients with respect to its antihypertensive efficacy and incidence and severity of adverse effects. Both drugs caused similar blood pressure reductions without interfering with pulse pressure. The hypotensive effect of verapamil was not accompanied by any effect on heart rate, while after propranolol there was a significant bradycardia. ST-segment and T wave abnormalities at rest and after exercise were partially or completely reverted by both drugs. The incidence and severity of adverse effects was very low and no patient was withdrawn from the study because of complaints due to the active drugs. Verapamil can be compared as antihypertensive drug to the beta-blocker propranolol and this may justify, together with the absence of negative effects on lipids, blood sugar, serum electrolytes and renal function, its use as an antihypertensive drug of first choice.

Adult↗
PubMed1984

Effects of afferent renal nerve stimulation on renal hemodynamic and excretory functions.

In anesthetized cats (n = 9) renal afferent fibers were electrically stimulated for 11 min, and the response of the contralateral innervated kidney was compared with that of the ipsilateral denervated one. Before stimulation, renal blood flow, glomerular filtration rate, and water and sodium excretions were significantly lower in the innervated kidney than in the denervated one. Afferent renal nerve stimulation augmented arterial pressure and also increased sodium and water excretions from both kidneys without concomitant changes in glomerular filtration rates and renal blood flows. Absolute and percent changes in sodium and water excretions from the innervated kidney were similar to those observed in the denervated one. The same results were obtained in cats (n = 4) which underwent bilateral adrenalectomy to avoid the effect of circulating catecholamines. In another group of cats (n = 5), the increase in renal perfusion pressure due to the stimulation was prevented by an aortic snare: this resulted in a slight but equal decrease of all variables in both kidneys. These experiments do not show a reflex control of renal function from renal afferents.

Afferent Pathways↗
PubMed1984

Neural control of the kidney--are there reno-renal reflexes?

Circulatory, secretory (renin release) and excretory (tubular sodium and water reabsorption) renal functions are known to be under neural control exerted by sympathetic fibers. Influences on circulatory and secretory functions are modulated by vagally mediated reflexes originated from low pressure (or volume) receptors in the cardiopulmonary area. The possibility that reno-renal reflexes may also exist has raised interest recently. Mechanoreceptors and chemoreceptors have been described in the kidney, and electrophysiological evidence of reno-renal reflexes is available. However, electrical stimulation of afferent renal nerves has failed to reflexly influence circulatory, secretory and excretory functions of the contralateral kidney. Deafferentation studies have been more successful, however. Transient denervation of one kidney by renal nerve cooling is accompanied by reduction of sodium and water excretion from the contralateral kidney with negligible changes in blood flow and glomerular filtration rate. The contralateral antidiuretic activity is prevented either by denervation of the contralateral kidney or by interruption of the afferent fibers running in the spinal dorsal roots. This definitely shows that a reno-renal reflex exists, consisting in a tonic inhibition of contralateral sympathetic activity controlling tubular reabsorption of sodium and water, and renin release.

Afferent Pathways↗
PubMed1984

Hemodynamic effects of once a day administration of combined chlorthalidone and metoprolol slow-release in essential hypertension.

The effects of a fixed combination of chlorthalidone (25 mg) and metoprolol slow-release (200 mg) (CM) on 24 hour blood pressure (BP) and heart rate (HR) values and their variabilities were evaluated in 6 ambulant hypertensives by the Oxford method, to obtain continuous intra-arterial recording and by computer to have a beat-to-beat analysis of the data. Compared to pre-treatment values, average 24 hour HR and mean BP recorded after 7-10 days of once daily CM orally administration were reduced by 18.4 +/- 3.1 and 14.7 +/- 3.0%, respectively. The effects of CM were also evident during isometric and dynamic exercise, whose pressor and tachycardic responses were left unimpaired (BP) or were only slightly reduced (HR) by CM. The long- and short-term BP and HR variabilities (calculated as variation coefficients among and within half hours, and within minutes) were also left unaffected by CM. These findings indicate that once a day administration of CM effectively reduces BP and HR over the 24 hours, without interfering with cardiovascular homeostasis. The effective and persistent reduction in both these variables (as well as their occurrence during exercise) suggests that the antihypertensive action of this treatment is accompanied by a clear-cut reduction in cardiac work.

Administration, Oral↗
PubMed1984

Regulation of sodium and water excretions by neural renorenal reflexes in the cat.

The reduction in sodium and water excretion observed in the right kidney when the left kidney is subjected to transient denervation, is entirely abolished by bilateral section of the dorsal roots from T9 to L4, whereas section of the left dorsal roots only, at the same spinal level, does not affect the contralateral renal response to left renal nerve cooling. The possibility that the bilateral dorsal roots section abolished the response of the right kidney because the afferent fibres from the left kidney travel in the right dorsal roots was explored in the present study. Experiments were performed in anaesthetized cats in which reversible denervation of the left kidney was done by cooling of left renal nerves (for 10 min) after cutting the right dorsal roots from T9 to L4. Cooling of left renal nerves caused a large increase in sodium and water excretion from the left kidney and a prompt decrease in sodium and water excretion from the right kidney. During the cooling period arterial pressure did not change and glomerular filtration rate slightly increased in the left kidney only. The results obtained in this group of animals were not significantly different from those previously observed in sham-operated cats or in cats with section of left dorsal roots only. As the contralateral antidiuretic and antinatriuretic response to renal denervation survives dorsal root section on either side but is prevented by bilateral section, this demonstrates that the inhibitory renal afferent fibres responsible for this renorenal reflex are distributed bilaterally to spinal dorsal roots.

Animals↗
PubMed1983

Effects of blood-pressure measurement by the doctor on patient's blood pressure and heart rate.

Changes in blood pressure in 10 or 15 min periods during which a doctor repeatedly measured blood pressure by the cuff method were monitored by a continuous intra-arterial recorder. In almost all the 48 normotensive and hypertensive subjects tested the doctor's arrival at the bedside induced immediate rises in systolic and diastolic blood pressures peaking within 1 to 4 min (mean 26.7 +/- 2.3 mm Hg and 14.9 +/- 1.6 mm Hg above pre-visit values). There were large differences between individuals in the peak response (range, 4--75 mm Hg systolic and 1--36 mm Hg diastolic) unrelated to age, sex, baseline blood pressure, or blood-pressure variability. There was concomitant tachycardia (average peak response 15.9 +/- 1.5 beats/min, range 4--45 beats/min) which was only slightly correlated with the blood-pressure rise. After the peak response blood pressure declined and at the end of the visit was only slightly above the pre-visit level. A second visit by the same doctor did not change the average size of the early pressor response or the slope of its subsequent decline.

Adolescent↗
PubMed1983

Plasma catecholamines do not invariably reflect sympathetically induced changes in blood pressure in man.

Plasma concentrations of noradrenaline and adrenaline were measured radioenzymatically in nine subjects during 4 min pressor and depressor responses (intra-arterial measurements) induced by increasing and reducing sympathetic vasoconstrictor tone via carotid baroreceptor deactivation and stimulation (neck chamber technique). During the pressor response (15 +/- 3 mmHg, mean +/- SE) plasma noradrenaline and adrenaline showed various changes in the different subjects and on average were not significantly increased above control. During the depressor response (-9 +/- 2 mmHg) plasma noradrenaline and adrenaline also showed various changes in the subjects and were on average not significantly reduced below control. In contrast the same subjects all showed an increase in noradrenaline and adrenaline (average 76 and 117%) at the fourth minute of a tilting manoeuvre with a return to pretilting values no more than 4 min after resumption of the supine position. These results suggest that the moderate and/or restricted alterations in sympathetic tone produced by manipulating a single baroreflex, though capable of affecting blood pressure, are not reflected by alterations in plasma catecholamines. To modify these humoral indices significantly, the more drastic or more diffuse alterations in sympathetic activity that may be produced by manipulating low as well as high pressure reflexogenic areas are needed.

Adult↗