A Nonpeptide Mimic of Bradykinin Blunts the Development of Hypertension in Young Spontaneously Hypertensive Rats

Abstract

Abstract —We tested whether FR190997 , a nonpeptide B 2 agonist, prevented the development of hypertension in young spontaneously hypertensive rats (SHR), which secrete less kallikrein into the urine than do Wistar-Kyoto rats. An intra-arterial (IA) injection of FR190997 (0.3 to 30 nmol/kg) caused dose-dependent hypotension in conscious Sprague-Dawley rats. Although the maximum hypotensive potency of FR190997 equaled that of bradykinin, its action lasted ≈10 times as long. Hoe140 (100 nmol/kg IA) significantly blocked the hypotensive response induced by FR190997 (10 nmol/kg). Atropine (100 nmol/kg IA) did not affect this response. A selective infusion of FR190997 into the renal artery induced natriuresis and diuresis in anesthetized rabbits. A continuous infusion (2 nmol · 10 mL −1 · h −1 per rat) of FR190997 into the abdominal aorta of young SHR (6 weeks old, n=6) for 6 days significantly ( P <0.05) reduced mean blood pressure to 114±6 (day 2) and 110±6 (day 5) mm Hg, from 149±7 and 162±6 mm Hg, respectively, in vehicle-infused rats (n=6). At 8 days after continuous infusion (day 14), mean blood pressure (148±5 mm Hg) in FR190997 -infused rats remained significantly ( P <0.05) lower than that in vehicle-infused rats (190±6 mm Hg), almost the peak value. The mesenteric artery isolated from FR190997 -treated rats (day 14) had lower contractile sensitivity to norepinephrine than that from vehicle-treated rats. These results suggested that the continuous infusion of a nonpeptide B 2 agonist may prevent hypertension if performed in the critical phase.