Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat.

Abstract

SUMMARY The angiotensin antagonist, saralasin, (10 and 30 rag/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 ± 0.4 to 16.2 ± 3.7 and 22.5 ± 2.4 ng/ml/hr (p < 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E, (PGE,) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Prorjranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p < 0.001). In sodium-depleted rats, saralasin (03 mg/kg) increased SRA from 12 ± 2 to 119 ± 6 ng/ml/hr (p < 0.001) and decreased blood pressure by 6% (p < 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE, by 79%, and arachidonate-induced hypotension by 81%.These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling All-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor. angiotensin system, suppresses the release of renin by a negative feedback mechanism resulting from its direct action on the juxtaglomerular cells.

Blockade of nitric oxide formation inhibits the stimulation of the renin system by a low salt intake

“…Meclofenamate also did not change plasma renin activity during intake of a low salt diet, suggesting that prostaglandins were not primarily involved in the stimulation of renin secretion and of renin gene expression by a low salt intake. This finding thus confirms the results of previous studies reporting that cyclooxygenase inhibitors do not lower plasma renin activity stimulated by a low salt intake in humans [14], dogs [16] or rats [4] as long as glomerular filtration is not diminished [7]. Fig.…”

Role of Renal Prostaglandins in Sympathetically Mediated Renin Release in the Rat

“…Thus, PG are thought to participate as mediators of intrarenal baroreceptor-stimulated renin release. PG synthesis inhibitors will not, however, inhibit the renin release due to sodium depletion, which is dependent upon a macula densa mechanism (40,41). Whereas PG participation in sympathetically mediated renin release has not been directly studied, indomethacin was found to inhibit several forms of renin release which were known to possess a beta-adrenergic component to their mechanism (hemorrhage, upright posture, etc.)…”

Role of renal prostaglandins in the control of renin release.

“…Again, it is important to recall that anesthesia and acute laparotomy stimulate basal levels of renin and prostaglandin release (Davis and Freeman, 1976;Terragno et al, 1977). Two separate studies in the conscious sodium deplete rat reported only partial (Suzuki et al, 1981b) or no attenuation (Campbell et al, 1979b) of the hyperreninemia after indomethacin administration.…”