Dexamethasone-inhibitable stimulation of plasma prorenin by ketamine in cats.
Plasma prorenin in humans is derived from both renal and extrarenal sources, but in the cat most plasma prorenin is normally of renal origin. Sodium depletion and beta-adrenergic blockade can increase plasma prorenin in cats, but the effects of sedatives and glucocorticoids are unknown. We examined the effect of ketamine, a centrally acting nonbarbiturate anesthetic, and of the glucocorticoid dexamethasone on plasma prorenin and renin. Intramuscular injection of ketamine (20 mg/kg, three times a day) for 4 days increased plasma prorenin slowly and consistently, from 7.4 +/- 1.4 (+/- SEM) to 11.4 +/- 2.2, 17.1 +/- 2.5, 20.2 +/- 3.0, and 29.2 +/- 3.4 ng/ml.h (P less than 0.001) on days 1, 2, 3, and 4, respectively, without any effect on plasma active renin. Plasma renin substrate and cortisol were also unchanged. Bilateral nephrectomy reduced both baseline and stimulated plasma prorenin to undetectable levels. Treatment with alpha 1-blocker, beta 1-blocker, angiotensin-converting enzyme inhibitor, or Ca2+ antagonist did not affect the rise in prorenin induced by ketamine, but dexamethasone completely blocked the response. In contrast, dexamethasone alone had little effect on plasma prorenin. These results demonstrate that repetitive ketamine administration selectively increases plasma prorenin, suggesting that renal prorenin secretion may be regulated independently of active renin. Blockade of stimulated, but not baseline, plasma prorenin by dexamethasone is consistent with a negative effect of glucocorticoids on the regulatory elements of the renin gene.
Rubattu
S
S
Cardiovascular Center, Cornell University Medical College New York, New York 10021.
Marion
D N
DN
Peterson
M
M
Sealey
J E
JE
D000818:Animals; D002415:Cats; D003907:Dexamethasone / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000097:blood* / Q000378:metabolism; D005260:Female; D007649:Ketamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D012083:Renin / Q000097:blood* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D004792:Enzyme Precursors; D007649:Ketamine; D003907:Dexamethasone; D014700:Verapamil; D012083:Renin; D011224:Prazosin