Renal interactions between norepinephrine and calcium antagonists

Abstract

The combined action of norepinephrine and calcium antagonists on the glomerular filtration rate (GFR) of isolated rat kidneys perfused at a constant pressure of 105 mm Hg was studied. Norepinephrine, 74 +/- 9 ng/ml (mean +/- SEM), increased the renal vascular resistance (RVR) by 50% and GFR declined by 88% (P less than 0.001). The subsequent addition of either diltiazem or verapamil (5 microM) returned RVR nearly to control and increased the GFR by an average of 86% over control (P = 0.007). Diltiazem or verapamil alone had little effect on RVR or GFR. Norepinephrine (20 ng/ml) did not affect RVR or GFR. In the presence of diltiazem, norepinephrine (20 ng/ml) again did not affect RVR but increased GFR by 58% (P = 0.003). With a low-calcium perfusate containing 0.4 mM total calcium, norepinephrine (90 ng/ml) did not affect RVR or GFR. Increasing perfusate norepinephrine to 236 +/- 8 ng/ml elicited a 50% increase in RVR, and GFR decreased by 95% (P less than 0.001). The subsequent addition of verapamil increased GFR to 2.8 times the original baseline value (P = 0.011) and restored RVR to control levels. These data suggest that diltiazem and verapamil block the vasoconstrictor action of norepinephrine on afferent arterioles selectively. Renal vascular sensitivity to norepinephrine decreases markedly either when the extracellular calcium concentration is reduced or in the presence of a calcium antagonist. However, a low-calcium perfusate does not mimic the property of calcium antagonists to facilitate an increase in GFR in the presence of norepinephrine.