Effect of indomethacin on the adrenal renin response to nephrectomy in the rat

The role of prostaglandins in the control of adrenal renin in vivo was evaluated in nephrectomized rats. Nephrectomy increased adrenal renin from 13.2 +/- 1.37 ng angiotensin I/mg protein/hr to 166.5 +/- 17.3 ng angiotensin I/mg protein/hr. Indomethacin treatment significantly suppressed the adrenal renin response to nephrectomy. (47.8 +/- 5.22 ng angiotensin I/mg protein/hr). Adrenal aldosterone was also suppressed by indomethacin. Adrenal prostaglandin E2 increased after nephrectomy and decreased after indomethacin. Plasma corticosterone and serum potassium did not change after indomethacin. These data indicate that inhibition of prostaglandin synthesis by indomethacin partially blocks the adrenal renin response to nephrectomy, suggesting that prostaglandins may play a role in the adrenal response to nephrectomy.     

Effect of indomethacin and propranolol on the blood pressure and renin response to atriopeptin III in conscious rats

The effect of prostaglandin synthesis inhibition and of beta-adrenoceptor blockade on the blood pressure and renin response to the synthetic atrial natriuretic peptide atriopeptin III was assessed in unanesthetized normotensive rats. This peptide was infused i.v. for 30 min at a rate of 1 microgram/min in rats pretreated either with indomethacin (5 mg i.v.) or propranolol (1 mg i.v.). The blood pressure reducing effect of atriopeptin III was attenuated neither by indomethacin nor by propranolol. Atriopeptin III per se did not modify plasma renin activity. Both the administration of indomethacin and of propranolol had a suppressing effect on renin release during atriopeptin III infusion. These data suggest that the vasodilating properties of atrial natriuretic peptides do not depend in the conscious normotensive rats on the production of prostaglandins. They also provide evidence that during infusion of such peptides, both prostaglandins and beta-adrenergic mechanisms are still involved in the regulation of renin secretion.     

Effects of adrenalectomy and nephrectomy on adrenal regeneration hypertension in the rat.

The involvement of the regenerating adrenal gland and kidney, and the contribution of deoxycorticosterone (DOC) and prostaglandin E2 (PGE2), in the development of adrenal regeneration hypertension (ARH) was evaluated in young female Sprague-Dawley rats. Based on tail-cuff plethysmographic measurement, animals subjected to nephrectomy and adrenalectomy on the right side and adrenal enucleation (removal of the adrenal cortex) on the left side developed significant (P less than 0.05, n = 12) hypertension within 6 weeks following operation. Subsequent left nephrectomy in these ARH rats produced a further elevation, whereas a secondary adrenalectomy resulted in an acute and discernible reduction in blood pressure within 24-36 hours. It is interesting to note that the progressive increase in blood pressure following left nephrectomy was significantly reversed by PGE2 (10 or 20 micrograms/kg, i.p.). At the same time, the reduction in blood pressure after secondary adrenalectomy was significantly retarded by deoxycorticosterone trimethylacetate (2 mg/kg, i.p.). These data demonstrated that both the kidney and the regenerating adrenal cortex are involved in the pathogenesis of ARH. Furthermore, it is probable that the secretion of DOC by the regenerating adrenal cortex is responsible for the elevation in blood pressure, in a process that is balanced by PGE2, possibly secreted by the kidney.     

Effect of prolonged ACTH stimulation on adrenal renin and aldosterone

Changes in adrenal renin, which have been regarded as mediator of aldosterone secretion in the adrenal gland, following prolonged ACTH treatment were investigated in male Wistar rats. After 2 days of daily sc injection of ACTH (Cortrosyn-Zinc, 50 micrograms/day), parallel increases in adrenal renin and aldosterone, and plasma aldosterone (PA) were induced. The plasma renin activity (PRA) was slightly but not significantly decreased. Prolonged treatment with ACTH for 8 days increased the adrenal renin, causing a marked reduction in the adrenal aldosterone concentration. The degree of decrease in the PRA was again not significant and similar to that after 2 days of ACTH treatment. Contrary to previout reports which have indicated participation of adrenal renin in the regulation of aldosterone secretion in the adrenal gland, the present results showed reciprocal changes in adrenal renin and aldosterone after prolonged treatment with ACTH. The present findings suggest a complicated relation between adrenal renin and aldosterone secretion in the adrenal gland.     

Effect of atrial natriuretic peptide on adrenal renin and aldosterone

The effect of atrial natriuretic peptide (ANP) on adrenal renin and aldosterone was investigated in anesthetized rats. Under pentobarbital anesthesia 40 mg/kg), intravenous infusion of ANP (0.25 micrograms/kg/min) for 45 min failed to alter the adrenal renin, adrenal aldosterone, and plasma aldosterone (PA). In this condition, intraperitoneal injection of ACTH (10 micrograms/kg) significantly increased the adrenal renin (from 2.4 +/- 0.1 to 5.0 +/- 0.08 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 13.6 +/- 1.3 to 22.7 +/- 2.3 ng/mg protein, P less than 0.01) and PA (from 59.8 +/- 5.8 to 75.5 +/- 7.4 ng/dl, P less than 0.05), respectively. Under ACTH stimulation, ANP infusion induced significant decreases in adrenal renin (from 5.0 +/- 0.08 to 2.8 +/- 0.2 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 22.7 +/- 2.3 to 16.2 +/- 1.8 ng/mg protein, P less than 0.05) and PA (from 75.5 +/- 7.4 to 61.6 +/- 4.9 ng/dl). These results suggest a possible role for adrenal renin in the mechanism underlying the inhibitory effect of ANP on aldosterone production in vivo.     

Effect of L-dopa and bilateral nephrectomy on the aldosterone response to metoclopramide

The dopaminergic antagonist, metoclopramide (MCP) causes an increase in plasma aldosterone (PA) by a processnot well delineated. To investigate the mechanism of action of metoclopramide (MCP), studies were performed in rats after pre-treatment with L-dihydroxy-phenylalanine (L-dopa) and after bilateral nephrectomy. Intra-arterial MCP (200 μg/kg) resulted in a significant elevation in PA and prolactin (PRL) at 5 min and plasma renin activity (PRA) at 10 min without altering serum potassium levels. Pre-administration of L-dopa (30 mg/kg) delayed and markedly blunted PA, PRL and PRA resonses to MCP. In 7 rats, studied 30 hours after bilateral nephrectomy, the PRA was measurable (2.5 ± 0.4 ng/ml h^?1) but displayed no response to MCP. In contrast, the PA and PRL responses to MCP were not significantly affected. L-dopa induced suppression of PRA and PA was prevented by pre-administration of MCP. These results suggest that dopaminergic modulation of PA secretion occurs independently of the renin-angiotensin system.     

The response of rat adrenal medulla to oxytocin

Effects of oxytocin (OT) on the adrenal chromaffin tissue of male rats were examined by coupled morphometric and biochemical techniques. Synthetic OT was administered in doses of 0.14 and 0.25 IU/100 g/d during 7 or 10 consecutive days and the effects were followed 1, 24, 72 and 168 hours after the last injection. The function and structure of chromaffin cells were affected by the higher dose of OT only. They caused divergent responses on their amine contents. Adrenaline, noradrenaline and dopamine contents were increased, while serotonin content was decreased. These changes were different in duration and time of incidence. Stereological analysis showed an enhanced number of chromaffin cells and an increase in their total volume. The parallelism between the changes in chromaffin cell number and the catecholamine content strongly suggests a mitogenic effect of the applied OT.     

Role of adrenal steroids on the cardiac c-AMP response to isoprenaline in the rat

The effect of adrenalectomy on the basal cardiac c-AMP level and the elevated c-AMP level induced by intravenous administration of isoprenaline (10 mcg/kg) were determined by radio-protein assay. The basal cardiac c-AMP level was not altered by adrenalectomy. But the cardiac c-AMP responses to isoprenaline was significantly less in adrenalectomized rats, maintained with 1% sodium chloride solution for one week; this effect, however, disappeared when animals were maintained for 2 or 4 weeks. This could not be restored by acute administration of dexamethasone (100 mcg/rat). The possible reasons for these effects of adrenalectomy are discussed.     

Effect of prolonged exhausting exercise on the adrenal cortex response to ACTH

Plasma cortison response of ACTH injection was studied in dogs under control conditions and after a prolonged exercise performed until exhaustion. Exercise induced a marked increase in plasma cortisol concentration but no significant differences were found in the level of plasma cortisol following ACTH injection between the control and post-exercise animals.     

Effect of prostaglandin inhibition by indomethacin on plasma active and inactive renin concentration in men.

The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (p = 0.004), total (p less than 0.001), and inactive (p = 0.02) renin at rest recumbent on average by 42, 19, and 8%, respectively, and at rest sitting on average by 45, 15, and 3%, respectively. Inhibition of prostaglandins with indomethacin reduced (p less than 0.001) active and total renin at each level of work load but not (p = 0.32) inactive renin. However, the exercise-induced stimulation (p less than 0.05) of active and total renin still occur during indomethacin. Indomethacin reduced (p less than 0.001) at rest sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2 by 50 and 54%, respectively, prostaglandin F2 alpha by 36 and 39%, respectively, and 13,14-dihydro-15-keto-prostaglandin F alpha by 38 and 60%, respectively. The urinary excretion of immunoreactive prostaglandin E2 and F2 alpha was also reduced.     

Effect of unilateral nephrectomy in mice on the level of the humoral immune response to T-independent antigen

The influence of unilateral nephrectomy on the degree of humoral immune response to T-independent (polyvinylpyrrolidone, PVP) and T-dependent (sheep red blood cells, SRBC) antigens was studied. The increase in the number in antibody-forming cells (AFC) and nonspecific immunoglobulin-forming cells (nIFC) was investigated by means of the adaptive transfer model. The lethally irradiated recipients were injected with the antigen and also the spleen cells of operated and intact donors. PVP did not induce significant alterations of antibody genesis in mice receiving spleen cells of unilaterally nephrectomized animals comparing with recipients of intact spleen cells. At the same time, the kidney operation induced the increase in the number of AFC and nIFC when the SRBC were used. Hence the activation of humoral immune response induced by kidney operation was related not to the direct activation of B-lymphocytes but to T-cells. The possible causes of this activation were analyzed. Spleen cells of operated animals enhance both specific and antigen-dependent nonspecific immune response.     

Effect of propranolol on plasma renin activity, renal cortex renin, and adrenal and brain isorenins in rats.

Propranolol administration to rats was studied for its effects on plasma renin activity, renal renin content, and adrenal and brain isorenins. Propranolol was given intraperitoneally at 6 and 30 mg/kg/day for a 15-day period. Pulse rate was significantly decreased. There were no effects on the isorenin content of adrenal or brain tissue or on renal renin content. Rats responded in two completely different ways with respect to plasma renin activity. Two-fifths had a total suppression of plasma renin activity; the rest had concentrations similar to those in controls. These observations are consistent with those seen during chronic administration of propranolol to hypertensive patients and suggest that its antihypertensive effect may in some patients be through the suppression of renin release. Its mechanism of action in most patients remains at present unclear.