Effect of bradykinin B₂ receptor antagonist and indomethacin on natriuretic and hypotensive responses to atrial natriuretic factor

Abstract

The effects of inhibition of bradykinin and prostaglandin on the renal and blood pressure responses to atrial natriuretic factor (ANF) were studied in anesthetized rats. Intraarterial infusion of the receptor antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin (BKA) at 14 micrograms/min, a rate sufficient to block the hypotensive response to 250 micrograms of bradykinin, did not affect the natriuresis due to injection of ANF (UNaV: control, before ANF, 393 +/- 101, after ANF, 2322 +/- 400 nmol/min; BKA, before ANF, 261 +/- 72, after ANF, 2259 +/- 390 nmol/min). In contrast, infusion of indomethacin (Indo) reduced the level of sodium excretion both before and especially after ANF administration (UNaV: Indo, before ANF, 75 +/- 15, after ANF, 320 nmol/min). The effect of combining BKA with Indo was not different from the effect of Indo alone (UNaV: BKA + Indo, before ANF, 119 +/- 26, after ANF, 469 +/- 167 nmol/min). The bradykinin antagonist, with or without Indo, was associated with significant hypotension relative to control. Indo, both in the absence and presence of the antagonist, was associated with a progressive decrease in blood pressure compared with control. However, in each the hypotensive responses to ANF were not different from those in the control group. We conclude that under the present experimental conditions bradykinin does not modify ANF-induced natriuresis. However, inhibition of prostaglandin synthesis by Indo is associated with renal salt retention, reducing natriuresis both before and after ANF administration.