Angiotensin-(1-7) induces bradykinin-mediated hypotensive responses in anesthetized rats

Angiotensin-(1-7) [Ang-(l-7)] reportedly potentiates hypotensive responses to bradykinin. We studied whether increases in circulating bradykinin would alter responses to Ang(1-7). In rats anesthetized with thiobutabarbital, bradykinin infusion (5 mu g/kg per minute IA) resulted in a rapid decrease in mean arterial pressure (MAP) of about 20 mm Hg (P<.01, n=9), although MAP slowly increased by 10 mm Hg after 15 minutes. When Ang-(l-7) (20, 80, and 380 nmol per rat IA) was given during bradykinin infusion, it elicited hypotension at 80 and 380 nmol (Delta MAP: -15+/-2.7 and -21+/-3.3 mm Hg, respectively; P<.001); this hypotension was not affected by the angiotensin type 1 antagonist L-158,809 (200 mu g/kg IA), the angiotensin type 2 antagonist PD 123319 (10 mg/kg LA), saralasin, or sarthran (10 mu g/kg per minute). The bradykinin type 2 receptor antagonist icatibant (30 mu g per rat) eliminated the hypotensive responses to Ang-(1-7), which now increased MAP at all doses tested (P<.005). Thus in the presence of bradykinin, Ang-(1-7) induces hypotensive responses that are blocked by icatibant and unaffected by angiotensin receptor antagonists. Ang-(1-7) given to saline-infused rats elicited hypertensive responses at all doses (Delta MAP: 6.4+/-1.5, 12+/-1.6, and 16.3+/-2.7 mm Hg, respectively; P<.01); these responses were abolished by L-158,809 and sarthran. In rats pretreated with saralasin, Ang-(1-7) induced hypotension at 80 and 380 nmol (Delta MAP: -7.7+/-2.3 and -9.5+/-2.7, respectively; P<.05), whereas icatibant abolished this response. Thus in the rat, Ang-(1-7) can decrease blood pressure by a mechanism involving the bradykinin type 2 receptor and participates with bradykinin in a vasodepressor pathway that may serve a counterregulatory role, modulating the vasoconstrictor effects of Ang II.