K-ATP CHANNELS ARE NOT ESSENTIAL FOR PRESSURE-DEPENDENT CONTROL OF RENIN SECRETION

This study aimed to investigate the functional role of ATP-sensitive K + (K+) channels in the control of renin secretion by renal perfusion p ressure. We studied the effect of openers and blockers of K-ATP-channe ls on basal-and low-pressure-induced renin secretion from isolated per fused rat kidneys (IPRK). Cromakalim (0.1-10 mu M) stimulated basal re nin secretion up to threefold and caused vasorelaxation in the IPRK. B oth effects of cromakalim were attenuated by glibenclamide. Cromakalim stimulated renin secretion from isolated juxtaglomerular (JG) cells a nd from microdissected afferent arterioles, all of which suggests that K-ATP channel openers stimulate renin secretion at the level of JG ce lls. A de crease in the perfusion pressure from 13.3 to 9.33 kPa (100 mmHg to 70 mmHg) increased renin secretion twofold, and cromakalim fur ther increased renin secretion. At 5.33 kPa (40 mmHg) renin secretion was increased sevenfold and was not further enhanced by cromakalim. Th e low-pressure-induced stimulation of renin secretion was not changed by glibenclamide. Finally, the dependence on calcium of the cromakalim -induced stimulation of renin was examined. Addition of the calcium an tagonist amlodipine to the perfusate stimulated renin secretion, and i n this situation cromakalim had no further effect. The stimulation of renin secretion by cromakalim in the IPRK was markedly attenuated by a ngiotensin II (1 nM). These results suggest that cromakalim could stim ulate renin secretion through a pathway that includes a decrease in JG cell calcium. K-ATP channels are not essentially involved in pressure -sensitive renin secretion.