Renal prostaglandins and the control of renin release.

Abstract

multifactorial. Stimuli for renin release act through three groups of mechanisms which include: 1) two intrarenal receptors, the renal vascular receptor in the afferent arteriole and the macula densa; 2) the renal nerves and a renal 0-adrenergic receptor; and 3) a group of humoral agents.1 In the past decade, attention has been focused on the potential role of the renal prostaglandins in renin release, both as primary stimuli*" 1 and as essential mediators in stimulus-secretion coupling for the renal vascular receptor, M the macula densa, 7 '• and the renal /3-adrenergic receptor. 8 ' 8> 101 lI It seems likely that the renal prostaglandins function as primary stimuli for renin release, both by a direct action on the juxtaglomerular (JG) cells 2 "* and possibly also by an indirect action to amplify or attenuate the signal for other receptor mechanisms, i.e., prostaglandins alter both urinary electrolyte excretion and renal arteriolar tone 4 -ia and thus might indirectly influence the macula densa and the renal vascular receptor, respectively. More controversial is the concept of the renal prostaglandins as essential mediators in stimulussecretion coupling for one or more of the basic receptor mechanisms in the control of renin release.11 The fundamental importance of the autonomous renal vascular receptor mechanism for renin release led to early studies of its relationship to the renal prostaglandins, and one of the first suggestions that prostaglandins function as mediators for stimulus-secretion coupling was for the renal vascular receptor." In adrenalectomized dogs with a single denervated nonfiltering kidney, a preparation in which the renal vascular receptor is isolated from the sympathetic nervous system and the macula densa," renal vein renin was increased both by reducing renal perfusion pressure and by intrarenal infusions of sodium arachidonate.8 Pretreatment with indomethacin was reported to block the renin responses to both stimuli, and it was suggested that renal vascular receptor stimulation of renin release is mediated by a cyclooxygenase product, presumably a prostaglandin.' These acute experiments* were performed in anesthetized dogs following surgery, conditions that stimulate basal levels of renin and prostaglandin release.

Relationship between PGE2 and renin release in dog kidneys Effects of afferent arteriolar dilation and adrenergic stimulation

“…The rise in renin release was attributed to renal ischemia or to strong activation of renin release mechanisms overcoming the inhibitory effect of indomethacin at low perfusion pressure. However, sympathetic stimulation probably became more intense as the renal arterial perfusion pressure was lowered in the conscious dogs studied by Freeman et al (1982) and in the anesthetized dogs with innervated kidneys studied by Blackshear et al (1979). In support of this explanation, Romero et al (1976) found a large increase in renin release in rabbits after extensive bleeding both before and after indomethacin administration.…”

“…That prostaglandins and 8-adrenergic agonists are independent stimulators of renin release may explain the observations of Blackshear et al (1979) in studies on anesthetized dogs and of Freeman et al (1982) on conscious dogs. Both groups observed that indomethacin inhibited renin release during reduction in the renal arterial perfusion pressure only within the range of autoregulation.…”

“…A relationship between renin release and prostaglandin synthesis has been suggested in several recent studies, although the evidence is indirect, based on examinations of renin release before and after infusion of inhibitors of prostaglandin synthesis. Blackshear et al (1979) and Freeman et al (1982) found that administration of inhibitors of prostaglandin synthesis prevented the rise in renin release in dogs during reduction of renal arterial perfusion pressure within the range of autoregulation. However, further reduction of perfusion pressure raised renin release as before inhibition of prostaglandin synthesis.…”