Renin release by rat kidney slices incubated in vitro. Role of sodium and of alpha- and beta-adrenergic receptors, and effect of vincristine.

Abstract

SUMMARYThe role of sodium concentration, of a-and /3-adrenergk receptors, and of a microtabolar inhibitor (vincristine) on renin release was studied in rat kidney slices ia vitro. Renin release was an active, linear, and temperature-dependent process. Kidneys from youag rats released ranch more renin thaa those from adults. Lowering sodium concentration inhibited renin release by one-half, even when osmolality was kept constant. Isoproterenol (10 ' to 10 ' M) stimulated reain release signifkaatJy in a partially dose-related manner, ^/-propranolol inhibited this stinralatioa. Significant (P < 0.05) inhibition of reain release was induced by /-epiaephrine or /-•oreplaephrine (10'° M). la the presence of aa a-receptor Mocking drag, pbeBoxybeazamine (10" • M), inhibition no longer occurred with epinephrine and stimulation was observed with /-aorepinephrine. Vutcristine (10** M) did not affect renin release when slices from the kidneys of normal rats or adrenalectomlzed, sodium-depleted rats were incubated, but significantly inhibited (P < 0.01) release that had been stimulated in vitro by isoproterenol. These results suggest to us that there may be (1) a direct or indirect (aiediated through the macula densa) effect of sodium on juxtaglomerular cells (2) an inhibitory role for a-adrenergic receptors on renin release, in addition to the stimulatory role of /3-receptors, (3) possible participation of microtubules in isoproterenol-stimulated renin release, and (4) an alternative mode of secretion of renin under stimulation by adrenalectomy and salt depletion.INCUBATION of kidney slices in vitro is a practical approach for studying the variables which affect renin secretion. However, even in this simple system, some points remain unsettled. For example, it is not clear whether sodium concentration of the incubation medium plays an important role, or whether changes in renin release observed after modifying sodium concentration actually depend only on changes in osmolality.1 " 8 Furthermore, although studies in vivo generally point to a stimulatory role of 0-adrenergic receptors on renin release,* there has been some controversy concerning the effect of catecholamines on renin release in vitro.7 "" Also, the role, if any, of a-adrenergic receptors still is to be elucidated. Finally, the mechanisms by which renin is released remain unknown. Since secretory granules containing renin have been shown in the epithelioid cells of the juxtaglomerular apparatus, 11 "" it is possible that secretion is mediated, as in other polypeptide-secreting cells, by the microtubular-microfilamentous system."Our present study was undertaken to clarify the effect of sodium in the incubation medium on renin release by rat kidney slices, as well as the role of a-and /8-adrenergic agonists and inhibitors. Furthermore, we tested the hypothesis that renin release is dependent on the microtubular system by studying the effect of a microtubular inhibitor, vincristine, on renin secretion. Methods INCUBATION OF KIDNEY SLICESMale Wistar rats (300-350 g...

Renin release from isolated rat glomeruli: effects of colchicine, vinca alkaloids, dimethylsulphoxide, and cytochalasins.

“…The present data on the effect of vinblastine on renin release are at variance with the effect on basal as well as isoprenaline induced renin release from kidney slices (Capponi & Valloton, 1976). The reason(s) for this apparent discrepancy is unclear but might be due to differences in the preparations used, such as, e.g.…”

Intracellular control of renin release — An overview

“…In addition, hormones known to mobilize calcium in several tissues such as angiotensin II, vasopressin and norepinephrine have been found to inhibit renin release by a calcium dependent process [10,16,77,79]. Using isolated juxtaglomerular cells, we could show that these hormones enhanced transmembrane calcium influx into the cells and led to a rise in the intracellular calcium concentration [45].…”

Stimulus-secretion coupling of renin. Role of hemodynamic and other factors.

“…The macula densa receptor responds to some yet unknown function of the fluid passing the distal nephron (Thurau, 1964;Vander, 1967;Kotchen et al, 1978). The neurogenic receptor, which presumably is on the juxtaglomerular cell membrane, stimulates renin secretion by a /?-adrenergic mechanism and inhibits by an a mechanism (Ganong, 1972;Vandongen et al, 1973;Capponi and Valloton, 1976). The vascular stretch receptor, presumably the juxtaglomerular cell itself, responds to the degree of stretch of the afferent arteriole such that a decreased stretch increases renin secretion (Tobian, 1960;Fray, 1976).…”