Mechanism of effect of diphenylhydantoin on renal renin release

Abstract

This study was undertaken to delineate the mechanism of the effect of diphenylhydantoin (DPH) on renal renin release. DPH at a dose of 0.18 mg X kg-1 X min-1 was infused for 30 min into the renal artery of anesthetized dogs with acute unilateral renal denervation. In the innervated kidney, DPH infusion increased renin secretion rate (RSR) from 189 +/- 54 to 939 +/- 279 ng ANG I X h-1 X min-1. In the contralateral denervated kidneys, RSR did not change. An identical study was done in a second group of dogs in which unilateral renal denervation was done 24 h prior to DPH infusion. In this group, DPH infusion increased RSR from 63 +/- 57 to 643 +/- 180 ng ANG I X h-1 X min-1 in the innervated kidneys. In the contralateral denervated kidneys, RSR did not change. In a separate group of indomethacin-treated nondenervated dogs, intrarenal infusion of DPH increased RSR from 131 +/- 32 to 452 +/- 88 ng ANG I X h-1 X min-1. The percent increase in RSR in the indomethacin-treated dogs was not significantly different from the non-indomethacin-treated dogs. These data suggest that the stimulatory effect of DPH on renin release is mediated by or requires the presence of renal nerves. The step(s) after the renal nerves is (are) not mediated by prostaglandins.

Mechanism of effect of dibutyryl cyclic adenosine 3',5'‐monophosphate on canine renal renin release.

“…The collections of the urine and blood samples were the same as described. shown by our laboratory to inhibit phenytoin-stimulated renin release (Cadnapaphornchai, Jones & McDonald, 1982) and renin release associated with ureteral obstruction (Cadnapaphornchai & McDonald, 1983 .E Fig. 1, group 1).…”

“…We therefore infused dibutyryl cyclic AMP into the renal artery superimposed on the intrarenal infusion of A23187. In our own laboratory this same dose of ionophore used has been shown to inhibit phenytoin-stimulated renin release (Cadnapaphornchai et al 1982) and renin release associated with ureteral obstruction (Cadnapaphornchai & McDonald, 1983). Therefore, the dose of ionophore used must have been adequate since it inhibits renin release in two different models.…”

“…min. This same dose of A23187 has previously been shown by our laboratory to inhibit phenytoin-stimulated renin release (Cadnapaphornchai, Jones & McDonald, 1982) and renin release associated with ureteral obstruction (Cadnapaphornchai & McDonald, 1983). 15-30 min later, dibutyryl cyclic AMP was infused into the same renal artery while infusion of A23187 continued.…”