A nonpeptide mimic of bradykinin blunts the development of hypertension in young spontaneously hypertensive rats.
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 approximately 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.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Hayashi
I
I
Inamura
N
N
Fujita
T
T
Ogino
M
M
D000367:Age Factors; D000758:Anesthesia; D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000819:agonists*; D012077:Renal Artery / Q000502:physiology; D012964:Sodium / Q000652:urine; D013047:Specific Pathogen-Free Organisms; D014556:Urine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C107104:FR 190997; D011804:Quinolines; D018002:Receptors, Bradykinin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012964:Sodium; D011188:Potassium; D009638:Norepinephrine