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 angiotensi n-(1-7) [Ang-(1-7)] on bradykinin (BK)-induced vasodilation in the mesenter ic vascular bed of anesthetized spontaneously hypertensive rats using intra vital microscopy. Topical application of BK and Ang-(1-7) induced vasodilat ion in mesenteric arterioles, The BK-induced effect, but not acetylcholine, sodium nitroprusside, or histamine responses, was potentiated in the prese nce of Ang-(1-7), This interaction was abolished by BK-B-2 and Ang-(1-7) an tagonists (HOE 140 and A-779, respectively), a K+ channel blocker (tetraeth ylammonium), and cyclooxygenase inhibitors (indomethacin and diclofenac); h owever, nitric oxide synthase inhibition (N omega -nitro-L-arginine methyl ester) did not modify the Ang-(1-7)-potentiating activity. Long-term angiot ensin-converting enzyme (ACE) inhibition increased BK and Ang-(1-7)-induced vasodilation. The BK potentiation by Ang-(1-7) was preserved after ACE inh ibition, Ang II type 1 receptor blockade, or the combination of both treatm ents. The most striking finding of this study was the unexpected observatio n that the potentiation of BK vasodilation in spontaneously hypertensive ra ts 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)-re lated mechanism in mediating BK potentiation by ACE inhibitors.