Churchill, MCDonald, Churchill, Journal of Pharmacology and Experimental Therapeutics (1979),2394 found that PHT (40-320 µM) stimulated renin secretion from rat renal cortical slices. The effect was blocked by incubating the slices in potassium-free medium and by ouabain (1 mM). The authors state that renin secretion is directly dependent on the transmembrane sodium gradient and that PHT stimulates secretion by increasing that gradient.

2394. Churchill, P. C., McDonald, F. D., Churchill, M. C., Phenytoin stimulates renin secretion from rat kidney slices, J Pharmacol., Exp. Ther., 211: 615-19,1979.

Migdal, Slick, Abu-Hamdan and McDonald, Journal of Pharmacology and Experimental Therapeutics (1980),1985 investigated the effect of PHT on renal hemodynamics and renin release in dogs. Infused into the renal artery (0.18 mg/kg/min.), PHT significantly altered renal hemodynamics, resulting in increased renal blood flow and decreased renal vascular resistance. Renin secretion was increased seven-fold. PHT also increased urine volume, sodium secretion and osmolar clearance. The authors conclude that PHT is both a natriuretic and a diuretic.

1985. Migdal, S. D., Slick, G. L., Abu-Hamdan, D. and McDonald, F. D., Phenytoin, renal function and renin release, J. Pharmacol. Exp. Ther., 215(2): 304-8, 1980.

Cadnapaphornchai, Pontes and McDonald, American Journal of Physiology (1984),2373 and Cadnapaphornchai, Kellner and McDonald, Federation Proceedings (1986),2372 in further studies, reported that PHT's stimulation of renin release is mediated through the renal nerves and by inhibition of alpha adrenoceptors. See Ref. 2371.

2371. Cadnapaphornchai, P., Kellner, D., McDonald, F., Role of adrenoceptor in diphenylhydantoin (D)-stimulated renal renin release, Fed. Proc., 44(5): 1570, 1985.
2372. Cadnapaphornchai, P., Kellner, D., McDonald, F. D., Inhibition of renal alpha adrenoceptor by diphenylhydantoin, Fed. Proc., 45(4): 1033, 1986.
2373. Cadnapaphornchai, P., Pontes, C., McDonald, F. D., Mechanisms of effect of diphenylhydantoin on renal renin release, Am. J. Physiol., 247(3): F418-22, 1984.

Cadnapaphornchai, Kellner and McDonald, Proceedings of the Society for Experimental Biology and Medicine (1989),3525 examined the effects of adrenergic blockers in PHT-stimulated renin release in five groups of anesthetized dogs. In their study, with the renal nerves intact, the authors demonstrated that prior treatment with the beta-1 adrenoceptor antagonists, metoprolol or atenolol, abolished PHT-stimulated renin release. Prior treatment with the beta-2 adrenoceptor antagonist ICI 118.551 had no effect on PHT-stimulated renin release. These findings suggest that PHT-stimulated renin release is mediated by beta-1 adrenoceptors.

3525. Cadnapaphornchai, P., Kellner, D., and McDonald, F.D., Role of adrenoreceptors in diphenylhydantoin-stimulated rennin release, Proc. Soc. Exp. Biol. Med., 190(4): 344-8, 1989.