Renin Release In Patients Research Articles

Effect of dibutyryl cyclic AMP on plasma renin activity in normal men and patients with primary aldosteronism

Dibutyryl cyclic AMP (DBcAMP) directly stimulates the release of renin from the juxtaglomerular (JG) cells in vitro. We investigated the effect of DBcAMP on plasma renin activity (PRA) in 6 normal men and in 8 patients with primary aldosteronism (PA). A 20-min infusion of 0.33 mg/kg/min of DBcAMP significantly increased PRA in normal men, but had little effect on PRA in patients with PA. Infusion of DBcAMP significantly reduced the blood pressure and the levels of serum sodium and potassium in normal men and the patients with PA. Infusion of DBcAMP significantly increased urine volume in normal men, but not in patients with PA. Urinary excretion of sodium increased in both groups after the infusion of DBcAMP. Thus, DBcAMP did not stimulate renin release in patients with PA, suggesting that the chronic excess production of aldosterone suppresses the release of renin from JG cells.

Effects of metoclopramide, a dopamine antagonist, on secretion of aldosterone and renin release in patients with primary aldosteronism.

To assess the interaction between dopamine and aldosterone secretion in primary aldosteronism, the dopamine antagonist, metoclopramide (methoxy-2-chloro-5-procainamide), was given as an i.v. bolus (10 mg) to 5 patients with primary aldosteronism and 5 normal subjects treated with dexamethasone (2 mg/day) to eliminate an influence of ACTH. Metoclopramide increased plasma aldosterone concentration (PAC) in primary aldosteronism from 39.1 +/- 15.5 to 42.5 +/- 15.9 ng/100 ml (p less than 0.05) and also from 12.9 +/- 2.3 to 23.6 +/- 3.4 ng/100 ml (p less than 0.01) in normal subjects at 15 min. Plasma renin activity (PRA), and plasma concentrations of cortisol, potassium, and sodium did not significantly change with metoclopramide in either primary aldosteronism or normal subjects. Plasma prolactin increased by 12- and 20-fold in primary aldosteronism and in normal subjects, respectively, but there was no significant positive correlation between changes in PAC and in plasma prolactin in either primary aldosteronism or normal subjects. It is suggested that dopamine inhibits the secretion of aldosterone in primary aldosteronism as well as in normal subjects. It seems unlikely that dopamine affects the release of renin in primary aldosteronism.

Dissociation of the effects of alpha 1-adrenergic blockade on blood pressure and renin release in patients with essential hypertension.

Prazosin, a selective antagonist of postsynaptic alpha-adrenoreceptors, was used to investigate the influence mediated by the juxtaglomerular alpha-adrenoreceptors on renin release in man. We studied, in seven patients with essential hypertension, the acute effects of 0.25 mg prazosin, given intravenously, on blood pressure and plasma renin activity, the degree of alpha-blockade induced by the drug being assessed by comparing the increments in blood pressure following a test dose of phenylephrine before and after prazosin administration. We also measured the increments in plasma renin activity in response to beta-adrenergic stimulus consisting of an isoproterenol challenge, before and during the prazosin induced alpha blockade. Prazosin infusion caused, within 20 min, a marked reduction of the pressor response to phenylephrine, a significant increment in plasma renin activity, and no change in blood pressure. The increments in renin in response to isoproterenol were significantly greater, both in absolute and percent values, after rather than before prazosin. These results indicate that the increase in renin during systemic alpha 1-adrenoreceptor blockade may be independent of the fall in blood pressure and support the view that the juxtaglomerular alpha 1-adrenoreceptors participate in the regulation of renin release with an inhibitory action, which antagonizes the stimulating influence of the beta-adrenoreceptors.

Role of renal prostaglandins in the mechanism of renin release in patients with essential hypertension

Role of renal prostaglandins in the mechanism of renin release in patients with essential hypertension

Essential hypertension: abnormal renal vascular and endocrine responses to a mild psychological stimulus.

We have assessed the influence of a mild emotional stimulus on arterial blood pressure, heart rate, renal blood flow, plasma renin activity (PRA), and plasma aldosterone concentration in 24 normal subjects, eight of who had a parent with hypertension, and in 15 patients with essential hypertension. A nonverbal IQ test, Raven's Progressive Matrices, was employed as the stimulus. In 11 of the 15 hypertensives, arterial blood pressure rose transiently by 7 mm Hg or more, but in only three of 16 normal subjects (x2 = 7.23, p less than 0.01). Transient moderate increases in heart rate were also more common in the hypertensives (p less than 0.01). Renal blood flow rose in 11 of 16 normal subjects and fell in each of the 15 patients with essential hypertension (x2 = 15.1; p less than 0.005). As opposed to the transient changes in arterial pressure and heart rate, the fall in renal perfusion was sustained. The PRA fell in 10 of the 16 normal subjects with a negative family history and rose in 14 of 15 patients with essential hypertension (p less than 0.005). Changes in plasma angiotensin II concentration and in plasma aldosterone were in accord with the changes in PRA, but plasma cortisol did not change. Both the renal vascular response and the change in PRA were intermediate in normal subjects in whom family history was positive for hypertension. For the entire group of 39 subjects there was statistically significant agreement between the direction of the renal vascular response and the directional change in PRA: renal blood flow rose when PRA fell and fell when PRA rose (p less than 0.005). We conclude that there is an abnormality in the control of both the renal circulation and of renin release in patients with essential hypertension in response to psychological provocation, and that a similar process is present in some normotensive subjects whose parents have hypertension.

Renin and aldosterone secretion in pheochromocytoma: Effect of chronic alpha-adrenergic receptor blockade

Patients suffering from pheochromocytoma characterized by an exclusive or almost exclusive excess of norepinephrine showed no (one patient) or only a moderate increase (two patients) in renin and aldosterone secretion. In those three patients with concomitant distinct hypersecretion of epinephrine, renin release (and aldosterone secretion except in one patient) was markedly enhanced. Similar results were obtained in a patient with excess norepinephrine and dopamine secretion. Renin release was markedly reduced in all patients during preoperative long-term alpha-adrenergic receptor blockade. With the exception of one patient, increased renin and aldosterone secretion was abolished. The results indicate that augmentation in renin release depends on the ratio of the different catecholamines secreted by the pheochromocytoma and their different effectiveness in stimulating beta-adrenergic receptors. Even in the presence of excess catecholamine secretion, there is evidence that renin secretion is predominantly mediated by beta receptors rather than by renal vascular alpha-adrenergic receptors. Normalization of catecholamine-induced enhanced renin release in patients with pheochromocytoma during chronic alpha-adrenergic receptor blockade supports the assumption that (alpha-) adrenergic blocking agents inhibit renin secretion distal to their blockade of specific adrenergic receptors. However, contrary to beta-adrenergic blockade, circadian rhythm of renin release seems to remain intact during alpha-adrenergic blockade.

Effect of ganglion-blocking agents on renin release in hypertensive patients.

In 18 patients with benign essential hypertension, renin release during reduction of arterial pressure due to sodium nitroprusside infusion was measured before and after administration of ganglion-blocking agents (pentolinium or trimethaphan). In 12 patients, renin release induced by reduction in pressure was significantly reduced but not abolished by ganglion blockade. Simultaneously, ganglion blockade significantly reduced renal vascular resistance (RVR) and almost abolished a decrease in renal blood flow (RBF) due to hypotension. In 6 other patients in whom no significant renin release resulted from hypotension, ganglion blockade caused little changes in renin release, RVR or RBF. The results support the hypothesis that renal sympathetic nerve activity is a factor in variations in renin release in patients with essential hypertension. Following ganglion blockade in the responsive patients, the significant reciprocal correlation between renal venous renin activity and sodium excretion rate shifted but still persisted, suggesting that the renin-releasing mechanism related to sodium excretion may be independent of innervation. On the other hand, the correlation between renin activity and the degree of reduction in pressure was insignificant after ganglion blockade. It is concluded that two intrarenal mechanisms, nerve-dependent and nerve-independent, are involved in renin release due to reduction in pressure. Ganglion blockade also exerted an inhibitory effect on renin release due to hypotension in 4 normotensive subjects and 5 patients with renovascular hypertension.

Renin release in patients with benign essential hypertension.

In 16 of 28 patients with benign essential hypertension, reduction of mean arterial pressure to 75 to 120 mm Hg by infusion of sodium nitroprusside caused significant increase in renin release estimated by the renal-systemic difference of renin activity and renal plasma flow (RPF). The threshold at which renin release increased was shifted to a range that was intermediate between that previously reported for normotensive subjects and that for patients with renovascular hypertension, but the average magnitude of renin release was almost comparable to that in normotensive subjects. In the other 12 patients, no significant renin release occurred during reduction in pressure of comparable degree. The difference in renin release was difficult to explain by the difference in severity of hypertensive disease or in sodium excretion, but increased renin release was usually associated with a decrease in RBF and a rise in renal vascular resistance, while insignificant release was usually associated with an insignificant change in RBF and a decrease in resistance. The average known duration of hypertension was significantly greater in the unresponsive patients. It is suggested that renal sympathetic nerve activity may be a factor in the variations in renin release in patients with essential hypertension.