AJP - Renal Physiology, Vol 247, Issue 4 650-F655, Copyright © 1984 by American Physiological Society
Na+-K+-ATPase inhibitors and renin release: relationship to calcium
M. Cruz-Soto, J. E. Benabe, J. M. Lopez-Novoa and M. Martinez-Maldonado
The inhibition of renin secretion and the vasoconstrictive action of
cardiac glycosides may be attributed to increases in cytosolic calcium as a
result of inhibition of Na+-K+-ATPase. These studies examined in the dog in
vivo the role of calcium on the renal actions of ouabain as assessed from
the modifying effects of calcium channel blockers. Since vanadate, another
Na+-K+-ATPase, inhibitor, enhances in vitro the binding of ouabain to
Na+-K+-ATPase, we examined the capacity of vanadate to modify the renal
effects of ouabain in vivo. Infusion of ouabain (1 microgram X kg-1 X
min-1) into the renal artery decreased RBF, GFR, and renin secretion, and
produced diuresis and natriuresis. When ouabain was infused in dogs
receiving the calcium channel blocker verapamil (100 microgram/min), it
failed to suppress renin secretion or cause renal vasoconstriction. In
addition, verapamil produced diuresis and natriuresis, which were greatly
enhanced by ouabain (e.g., verapamil FENa 12.0 +/- 1.1----34.2 +/- 5.1%).
The data strongly suggest that calcium entry into cells is a major mediator
of the renin inhibitory effect and of the renal vasoconstriction induced by
cardiac glycosides. The natriuresis observed during the calcium channel
blocker infusion suggests that this drug may have a direct tubular effect
on sodium reabsorption. Superimposition of vanadate (0.5 mumol/min) on
ouabain infusion led to massive natriuresis (FENa, 5 +/- 1----35 +/- 4%),
renal vasodilation (RBF 90 +/- 12----170 +/- 15 ml/min), and an increase in
renin secretion (delta, 100%).(ABSTRACT TRUNCATED AT 250 WORDS)
