Effects on blood pressure of intracerebroventricular administration of a kinin antagonist.
The components of the kallikrein kinin system are present in brain, and blood pressure is increased when kinins are injected into the brain cerebral ventricles. Therefore, brain kinins may play a role in the regulation of blood pressure. Kinin analogs which are effective as blockers of the vasodilatory and musculotropic activity of kinins have recently become available. Our objective in this study was to examine whether one of these kinin antagonists (K-ant) inhibits the pressor activity of intracerebroventricular (ICV) bradykinin, and whether ICV injections of this antagonist would alter basal mean blood pressure (BP). The analog used was DArg0-Hyp3-Thi5,8-DPhe7-bradykinin. All injections (10 microliters) were made into a lateral cerebral ventricle of restrained, conscious rats. The hypertensive response to 0.5 microgram bradykinin was partially blocked by simultaneous injections of either 5 or 10 micrograms of the K-ant: From (delta MBP = 36 +/- 7 to 17 +/- 5, p less than 0.05, and from 34 +/- 6 to 8 +/- 1 mmHg, p less than 0.01, respectively. Lower concentrations of K-ant were ineffective; the K-ant at doses up to 10 micrograms had no effect on BP. Doses of 25 and 50 micrograms increased BP (delta MBP = 32.5 +/- 5 and 59.0 +/- 5.5 mmHg, respectively, p less than 0.001). Both the 25 and the 50 micrograms doses of the K-ant induced barrel rotation in all rats. These data suggest that kinins present in circumventricular structures do not play a role in normal blood pressure regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
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XP
Henry Ford Hospital, Hypertension Research Division, Detroit, Michigan.
Carretero
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OA
Akahoshi
M
M
Scicli
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AG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
C053748:B 4162; D001920:Bradykinin