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Biomedical subjects

A Morganti

Publications and source records attributed to A Morganti.

At least 55 records · Page 3Linked to original sources

Plasma active and inactive renin and fetal complications in women with high risk pregnancies.

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.

Adult↗

Renal and humoral effects of ibopamine, a dopamine agonist, in patients with liver cirrhosis.

We investigated the renal and humoral effects of short-term administration of ibopamine, an orally active dopamine agonist, in patients with liver cirrhosis. The patients were divided into two groups on the basis of sodium excretion with a constant sodium intake of 40 mEq/d. We also compared the effects of ibopamine with those induced by intravenous infusion of dopamine hydrochloride (3 micrograms/kg per minute) in similar patients. Ibopamine caused significant increases in urine output, glomerular filtration rate, and sodium excretion throughout the 4 hours of the trial in patients with basal sodium excretion rate greater than 20 mmol/d. These renal effects were associated with a significant reduction in plasma aldosterone concentration. In contrast, only a transient increase in glomerular filtration rate and a diminution in plasma aldosterone concentration were observed after ibopamine in the patients with a basal sodium excretion rate less than 20 mmol/d. The infusion of dopamine had renal effects similar to those of ibopamine in both groups of patients. These results indicate that in cirrhotic patients with normal sodium excretion, ibopamine exerts a diuretic and natriuretic effect similar to that of dopamine infusion. However, these properties of dopaminergic agents are apparently lost in patients with avid sodium retention.

Adult↗

Investigation of reflexes from volume and baroreceptors during converting-enzyme inhibition in humans.

This article emphasizes the importance of testing baroreceptor and cardiopulmonary receptor control of circulation during angiotensin-converting enzyme (ACE) inhibitor treatment in hypertensives, because removal of angiotensin II-dependent stimulation of the sympathetic nervous system could impair reflex blood pressure homeostasis. In essential hypertensive subjects, the sympathetic vasoconstriction that occurs in skeletal muscle after deactivation of cardiopulmonary receptors was reduced after short-term or prolonged administration of the ACE inhibitor, captopril. However, another sympathetic target of the cardiopulmonary reflex, that is, renin release, was unaltered by both short-term and prolonged administration of captopril. Furthermore, the blood pressure and heart rate influences of arterial baroreceptors were preserved or even enhanced after administration of captopril. Thus important reflex mechanisms for cardiovascular homeostasis are not adversely affected by ACE inhibition, which preserves blood pressure levels during gravity challenges or exercise. Preliminary data suggest that this may be even more evident for benazepril.

Angiotensin-Converting Enzyme Inhibitors↗

Time-course of the changes in blood pressure and in plasma renin activity during the first week after dilation of renal artery stenosis.

We measured arterial pressure and plasma renin activity throughout the first week after a technically successful percutaneous transluminal renal angioplasty (PTRA) in 12 patients with hypertension and unilateral renal artery stenosis. Mean arterial pressure fell from 126 +/- 4 to 105 +/- 3 mmHg within 1-2 days of PTRA and stabilized thereafter; in addition, plasma renin activity decreased sharply during the first 2 days after the angioplasty (from 5.2 +/- 2.3 to 1.3 +/- 0.3 ng/ml per h) but continued to decline, reaching 0.8 +/- 0.2 ng/ml per h at the end of the study. When the antihypertensive effect of PTRA was examined in relation to baseline values of plasma renin activity, the patients with low, intermediate and high plasma renin activity showed percentage decreases in mean arterial pressure of, respectively, 6%, 16% and 19% by the sixth day of observation after the angioplasty. No overall correlation was found between the changes in arterial pressure and those in plasma renin activity induced by PTRA. These data suggest that the beneficial effect of PTRA on blood pressure can be estimated within a few days and that the reduction in the activity of the renin system is the principal but not the sole mechanism responsible for it.

Adult↗

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↗

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↗

Contribution of the renin-angiotensin system and of the sympathetic nervous system to blood pressure homeostasis during chronic restriction of sodium intake.

In a previous paper, we showed that during a long-term, moderate restriction in sodium intake, sympathetic nervous system activity was only transiently stimulated, whereas a sustained rise of plasma renin activity occurred. However, the contribution from stimulation of the renin-angiotensin system in the maintenance of blood pressure homeostasis during a low-salt diet is still unclear. To investigate this issue, in eight normal subjects blood pressure, heart rate, plasma catecholamines, renin activity, and aldosterone were measured during normal sodium intake (150 mEq/d), after converting-enzyme inhibition (enalapril 20 mg/d po), and during one month of sodium intake restriction (50 mEq/d) associated with chronic inhibition of converting-enzyme (CEI). During a low-salt diet with CEI, plasma renin activity rose significantly as a result of CEI. In addition, even in the presence of a marked and sustained increase in plasma norepinephrine and in upright heart rate, a decrease in blood pressure was observed in all the measurements performed during the course of the study as compared to the control values. Our findings support the hypothesis that renin-angiotensin system activation plays an important role in the maintenance of blood pressure homeostasis during a low-salt diet. In fact, in the presence of an effective blockade of angiotensin II formation, blood pressure is decreased, despite the concurrent, sustained stimulation of the sympathetic nervous system.

Adolescent↗

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↗

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↗

[Mechanisms of regulation of arterial blood pressure: role of the sympathetic nervous system and of the renin-angiotensin system in patients on a low-sodium diet].

In order to discover more about the role of the sympathetic nervous and renin-angiotensin systems in the preservation of homeostasis during chronic reductions of salt intake, blood pressure, blood catecholamines and renin activity were measured in a group of healthy subjects in normal conditions and on a salt-free diet combined with blockade of the conversion enzyme by enalapril. The results confirmed the hypothesis advanced on an earlier occasion i.e. that both hormone systems contribute to pressure during salt depletion in the initial phase, while over the long term only the renin-angiotensin system is activated though when this is inhibited, the sympathetic nervous system will take over its function.

Adolescent↗

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↗

Comparative measurements of immunoreactive renin, plasma renin activity and angiotensin II in human plasma.

In human plasma samples we compared the values of renin activity, determined with a conventional enzymatic assay, with those of immunoreactive renin, determined with a new, direct immunoradiometric assay which employs highly specific monoclonal antibodies, and with those of angiotensin II; the comparative measurements of renin were carried out also in trypsin activated samples of nephric and anephric subjects. We found that, overall, there was a close relationship between renin activity and immunoreactive renin; however, this relationship was absent when the statistical analysis was restricted to plasmas with low or very low renin. We also found that, within a rather wide range of values, angiotensin II was more closely correlated with immunoreactive renin than with renin activity. Trypsin activation increased to a similar extent immunoreactive renin and renin activity in plasma of nephric and anephric subjects and, overall, the values of total renin obtained with the two assays were significantly correlated. The results of these comparative determinations indicate that, in general, the measurement of immunoreactive renin represents a valid alternative to that of renin activity and a reliable index of the activity of the renin-angiotensin system. In addition, studies with trypsin activation suggest that even in the anephric state human plasma contains an inactive enzyme convertible into an active form which has immunological properties similar to those of active renin.

Angiotensin II↗

Effectiveness of Sepharose-bound trypsin versus liquid-phase trypsin plus benzamidine for activation of inactive renin in human plasma.

We compared the effectiveness of two techniques involving the use of the enzyme trypsin to activate inactive renin in human plasma. Both these methods were developed to optimize activation with trypsin by preventing the possible destruction of activated renin by trypsin itself. In one method, an antitryptic agent such as benzamidine is added to plasma, concomitantly with trypsin (liquid phase). In the other a low concentration of Sepharose-bound (immobilized) trypsin is used. In six plasma samples we have found that trypsin (1.5 mg/ml) activation, with or without benzamidine (0.8 mg/ml), yielded similar values of activated renin (11.0 +/- 2.7 vs. 11.3 +/- 2.3 ng/ml/hr). However, the addition of immobilized trypsin to pool plasma pretreated with trypsin plus benzamidine caused a further increase in plasma renin activity (PRA); in contrast, the addition of trypsin and benzamidine to pool plasma pretreated with immobilized trypsin caused a decrease in PRA. In 17 plasma samples from patients with essential hypertension we found that the inactive renin values were always higher after treatment with immobilized trypsin than with trypsin plus benzamidine (9.0 +/- 0.7 vs. 6.1 +/- 0.5 ng/ml/hr, P less than 0.01); moreover, there was a positive correlation between the differences in the values of inactive renin measured with the two methods and the values obtained with immobilized trypsin (r = 0.64, P less than 0.01). Therefore, the activation with immobilized trypsin is more effective than that with liquid-phase trypsin, alone or in combination with benzamidine, in converting inactive renin in human plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗