DISPARATE EFFECTS OF CALCIUM-CHANNEL BLOCKERS ON PRESSURE-DEPENDENCE OF RENIN SECRETION AND FLOW IN THE ISOLATED PERFUSED RAT-KIDNEY

Using the model of isolated perfused rat kidneys this study was performed to investigate whether or not voltage-operated calcium channels are essentially involved in the pressure control of renin secretion from the kidneys. At a perfusion pressure of 100 mm Hg (13.3 kPa) renin secretory rates were 4.2 +/- 0.7 (ng angiotensin I h-1) min-1 g-1. Stepwise reduction of renal perfusion pressure to 80, 60, and 40 mm Hg (10.6, 8.0, 5.3 kPa) resulted in an increase of renin release yielding a 30-fold stimulation at 40 mm Hg vs 100 mm Hg. Increasing the perfusion pressure above 100 mm Hg did not further significantly decrease renin secretion. The perfusate flow rate was also pressure-dependent. Flow rates increased linearly with pressure and reached a plateau at 100 mm Hg, which was maintained up to 160 mm Hg (21.3 kPa). The averaged flow rate at the plateau was 15.5 ml min-1 g-1. In the presence of the three different calcium antagonists nifedipine (5-mu-M), nitrendipine (3-mu-M) and verapamil (5-mu-M), myogenic autoregulation of flow was abolished as indicated by the rise of the pressure/flow curve between 40 and 160 mm Hg. At the same time, however, these calcium channel blockers did not alter the relationship between perfusion pressure and renin secretion. Moreover, the calcium channel agonist Bay K 8644 (5-mu-M) caused a strong and long-lasting vasoconstriction, without changing renin secretion. Taken together, our findings indicate that organic calcium antagonists at concentrations sufficient to block voltage-operated calcium channels in vascular smooth muscle cells have no influence on the pressure-dependent control of renin secretion. In consequence, it appears unlikely that voltage-operated calcium channels are essentially involved in the signal transduction mechanism that links renin secretion and blood pressure.