Angiotensin-(1-7) induces bradykinin-mediated hypotensive responses in anesthetized rats.
Angiotensin-(1-7) [Ang-(1-7)] 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 microg/kg per minute I.A.) 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-(1-7) (20, 80, and 380 nmol per rat I.A.) was given during bradykinin infusion, it elicited hypotension at 80 and 380 nmol (deltaMAP: -15+/-2.7 and -21+/-3.3 mmHg, respectively; P<.001); this hypotension was not affected by the angiotensin type 1 antagonist L-158,809 (200 microg/kg I.A.), the angiotensin type 2 antagonist PD 123319 (10 mg/kg I.A.), saralasin, or sarthran (10 microg/kg per minute). The bradykinin type 2 receptor antagonist icatibant (30 microg 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 (deltaMAP: 6.4+/-1.5, 12+/-1.6, and 16.3+/-2.7 mmHg, 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 (deltaMAP: -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.
Abbas
A
A
Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich 48202-2689, USA.
Gorelik
G
G
Carbini
L A
LA
Scicli
A G
AG
D000803:Angiotensin I; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004357:Drug Synergism; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D057911:Angiotensin Receptor Antagonists; D065168:Bradykinin Receptor Antagonists; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin