Effects of a kinin antagonist on mean blood pressure.
Administration of high doses of a kinin antagonist produces an increase in blood pressure. Thus, endogenous kinins may be involved in the regulation of blood pressure. Kinins can induce the release of vasoactive substances such as catecholamines, renin, vasopressin, histamine, and prostaglandins. To determine whether the blood pressure changes induced by high doses of kinin antagonist are due to agonistic activity mediated by these vasoactive substances, we studied the effect on blood pressure of a kinin antagonist (DArg0-Hyp3-Thi5,8-DPhe7-bradykinin) administered to control, nephrectomized, and adrenalectomized rats, and to rats treated with vasopressin V1-receptor antagonist, ganglionic and alpha- and beta-adrenergic receptor blockers (either separately or combined), histamine H1- and H2-receptor blockers, and indomethacin, a prostaglandin synthesis inhibitor. Blood pressure changes were monitored on awake, restrained rats. In the control rat, the kinin antagonist injected as a bolus (4 mg/kg) into the ascending aorta produced a transient biphasic blood pressure response, first a pressor effect (delta BP = 7 +/- 1 mm Hg; p less than 0.05), then a depressor effect (delta BP = -20 +/- 6 mm Hg; p less than 0.05). The pressor response to the kinin antagonist was not affected by any of the treatments; however, the depressor effect of the kinin antagonist appeared to be caused by the release of vasodilator prostanoids from the kidney, since it was not observed in the nephrectomized rats or in those treated with indomethacin. The pressor effect induced by the kinin antagonist suggests that kinins may contribute to the regulation of blood pressure.
Carbonell
L F
LF
Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
Carretero
O A
OA
Madeddu
P
P
Scicli
A G
AG
D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives*; D003243:Consciousness; D007668:Kidney / Q000502:physiology; D007705:Kinins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats
D007705:Kinins; D009842:Oligopeptides; C053748:B 4162; D001920:Bradykinin