Central nervous system kinin receptors and the hypertensive response mediated by bradykinin

Abstract

Bradykinin (Bk) administered intracerebroventricularly to the rat causes an increase in arterial pressure. Analogues of Bk with agonist and antagonist activity were injected, over a wide dose-range, into the posterior region of the fourth ventricle of unanaesthetized rats implanted with permanent ventricular canullae, and blood pressure was measured directly from the abdominal aorta. The analogues Ile-Ser-Bk (T-kinin) and Lys-Lys-Bk, which interact with both B1 and B2 Bk receptors, produced pressor effects similar to those of Bk, although of greater duration, whereas des-Arg9-Bk, a B1-receptor agonist, had no effect. The B1-antagonist des-Arg9-[Leu8]-Bk did not alter the Bk pressor response, but D-Arg-[Hyp3, Thi5,8,D-Phe7]-Bk, which interacts both with B1- and B2-receptors blocked the responses to Bk, T-kinin and Lys-Lys-Bk and caused parallel shifts to the right of the Bk dose-response curves. Neither antagonist, by itself, had any effect on blood pressure. It is concluded that the central pressor response to Bk is mediated by receptors of the B2 subtype.