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(Hypertension. 2000;35:437.)
© 2000 American Heart Association, Inc.

Scientific Contributions

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

Masataka Majima; Izumi Hayashi; Naoya Inamura; Tomoe Fujita; Michiko Ogino

From the Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

Correspondence to Masataka Majima, MD, PhD, Department of Pharmacology, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228, Japan.

Abstract—We tested whether FR190997, a nonpeptide B₂ 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 B₂ agonist may prevent hypertension if performed in the critical phase.

Key Words: rats, inbred SHR • bradykinin • natriuresis • hypertension, experimental • blood pressure

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