Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo.
In the present study, we investigated the potentiating effect of angiotensin-(1-7) [Ang-(1-7)] on bradykinin (BK)-induced vasodilation in the mesenteric vascular bed of anesthetized spontaneously hypertensive rats using intravital microscopy. Topical application of BK and Ang-(1-7) induced vasodilation in mesenteric arterioles. The BK-induced effect, but not acetylcholine, sodium nitroprusside, or histamine responses, was potentiated in the presence of Ang-(1-7). This interaction was abolished by BK-B(2) and Ang-(1-7) antagonists (HOE 140 and A-779, respectively), a K(+) channel blocker (tetraethylammonium), and cyclooxygenase inhibitors (indomethacin and diclofenac); however, nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester) did not modify the Ang-(1-7)-potentiating activity. Long-term angiotensin-converting enzyme (ACE) inhibition increased BK and Ang-(1-7)-induced vasodilation. The BK potentiation by Ang-(1-7) was preserved after ACE inhibition, Ang II type 1 receptor blockade, or the combination of both treatments. The most striking finding of this study was the unexpected observation that the potentiation of BK vasodilation in spontaneously hypertensive rats treated short- or long-term with ACE inhibitors was reverted by the Ang-(1-7) antagonist A-779. Our results unmasked a key role for an Ang-(1-7)-related mechanism in mediating BK potentiation by ACE inhibitors.
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Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
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D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects* / Q000503:physiopathology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014664:Vasodilation / Q000187:drug effects
C092006:7-Ala-angiotensin (1-7); D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C065679:icatibant; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin