EFFECTS OF FUROSEMIDE AND VERAPAMIL ON THE NACL DEPENDENCY OF MACULA DENSA-MEDIATED RENIN SECRETION

The present studies in perfused specimens of the juxtaglomerular appar atus microdissected from rabbit kidneys were performed to quantitative ly evaluate the relation between macula densa NaCl concentration and r enin secretion and to study the effect of furosemide and verapamil on NaCl dependency of renin release. Renin secretion was found to decreas e exponentially when macula densa NaCl concentration was increased fro m 26/7 mmol/L (Na/Cl) to 46/27, 66/47, and 86/67 mmol/L. Increasing Na /Cl concentrations from 86/67 to 106/87 mmol/L had no further effect o n renin secretion. [Cl](1/2), the chloride concentration producing the half-maximal effect, was 30 mmol/L. Addition of 50 mu mol/L furosemid e to the luminal fluid caused renin secretion to become essentially in dependent of macula densa NaCl concentration. This effect was due to b oth an increase of renin secretion at high NaCl concentrations and a d ecrease of renin release at low NaCl concentrations. Verapamil added t o the superfusate at a concentration of 1 mu mol/L also abolished NaCl dependency of renin secretion; most of this effect was due to an incr ease of renin release at high luminal NaCl. These results suggest that Na-2Cl-K cotransport and calcium flux through voltage-gated channels are two mechanisms required for the expression of NaCl-dependent renin release. Identification of the cellular localizations of these two cr itical membrane proteins in the renin control pathway requires further study.