Angiotensin-(1-7) potentiates the coronary vasodilatatory effect of bradykinin in the isolated rat heart

Abstract

It has been shown that angiotensin-(1-7) (Ang-(1-7)) infusion potentiates the bradykinin (BK)-induced hypotensive response in conscious rats. The present study was conducted to identify Ang-(1-7)-BK interactions in the isolated rat heart perfused according to the Langendorff technique. Hearts were excised and perfused through the aortic stump under a constant flow with Krebs-Ringer solution and the changes in perfusion pressure and heart contractile force were recorded. Bolus injections of BK (2.5, 5, 10 and 20 ng) produced a dosedependent hypotensive effect. Ang-(1-7) added to the perfusion solution (2 ng/ml) did not change the perfusion pressure or the contractile force but doubled the hypotensive effect of the lower doses of BK. The BK-potentiating Ang-(1-7) activity was blocked by pretreatment with indomethacin (5 mg/kg, ip) or L-NAME (30 mg/kg, ip). The Ang-(1-7) antagonist A-779 (50 ng/ml in Krebs-Ringer) completely blocked the effect of Ang-(1-7) on BK-induced vasodilation. These data suggest that the potentiation of the BK-induced vasodilation by Ang-(1-7) can be attributed to the release of nitric oxide and vasodilator prostaglandins through an Ang-(1-7) receptor-mediated mechanism.

Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat hearts

“…This finding is consistent with our observations on isolated hearts (18,20) and other preparations (for a review, see Ref. 13).…”

“…Under the same conditions, Ang II (27 and 70 nM) produced a significant reduction in coronary flow (39 and 48%, respectively) associated with a significant increase in force (17). In contrast, Almeida et al (18) have shown that in isolated rat hearts Ang-(1-7) induced an increase in the vasodilator effect of bradykinin (BK) through a nitric oxide (NO) and prostaglandin release-related mechanism.…”

The role of bradykinin, AT2 and angiotensin 1–7 receptors in the EDRF‐dependent vasodilator effect of angiotensin II on the isolated mesenteric vascular bed of the rat

“…Unlike other vascular beds, where A 779, a putative Ang 1-7 antagonist (Santos et al, 1994), inhibits the vasodilator effect of Ang 1-7 (Bayorh et al, 2002;Ren et al, 2002), our results demonstrate that the vasodilator effect of Ang 1-7 on the MVB could involve other receptors, given that A 779 does not inhibit Ang 1-7 vasodilation. BK appears to modulate Ang 1-7-induced vasodilation, since several reports have shown that the vasodilator effect of BK is enhanced by Ang 1-7 and vice versa (Brosnihan et al, 1996;Gorelik et al, 1998;Almeida et al, 2000;Fernandes et al, 2001;Tom et al, 2001). Also, the involvement of BK in the vasodilator effect of Ang 1-7 is suggested by Brosnihan et al (1996), who demonstrated that the vasodilator effect of Ang 1-7 was inhibited by HOE 140.…”

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

“…Furthermore, Ang-(1-7) elicited an increase in the vasodilator effect of BK in isolated perfused rat hearts. This effect was dependent on Mas and NO and prostaglandin release (Almeida et al 2000). Ang-(1-7) also evoked vasodilation in isolated perfused mouse hearts involving interaction of Mas with AT 1 -and AT 2 -related mechanisms (Castro et al 2005).…”

“…2). The signal transduction pathways following activation of Mas in the heart are not fully characterized, but probably involve release of prostacyclin and/or NO release (Almeida et al 2000, Ferreira et al 2001, Castro et al 2005 since Ang-(1-7) stimulated NO production and activated endothelial NO synthase (eNOS) and Akt in cardiomyocytes (Dias-Peixoto et al 2008). Of note, the antihypertrophic effects of Ang-(1-7) on Ang II-treated cardiomyocytes were prevented by the blockade of the NO/cGMP pathway .…”