Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo.
ABSTRACT 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.
Article: New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor axis.[show abstract] [hide abstract]
ABSTRACT: Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation. Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1-7). The axis formed by ACE2/Ang-(1-7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT(1) receptor. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and pulmonary system. Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis.International journal of hypertension. 01/2012; 2012:147825.
Article: Are multiple angiotensin receptor types involved in angiotensin (1-7) actions on isolated rat portal vein.[show abstract] [hide abstract]
ABSTRACT: Angiotensin (1-7) [Ang (1-7)] is a bioactive component of the renin angiotensin system. Ang (1-7) may interact with angiotensin type 1 (AT1) or type 2 (AT2) receptors and with Ang (1-7) - specific receptors. We examined the interactions between different doses of Ang (1-7) (1 nM-1 microM) and angiotensin II (Ang II) (10 and 100 nM) on isolated rat portal vein. In endothelium-denuded portal vein rings, Ang (1-7) inhibited contractile effects induced by Ang II. The effects of Ang (1-7) were modified by indomethacin, N(G)-nitro-L-arginine methyl ester (L-NAME), (D-Ala7)-Angiotensin (1-7) (H-2888) and losartan. Our results suggest that on rat isolated portal vein rings without endothelium, Ang (1-7) reduces Ang II-induced contractions by acting mostly on Ang (1-7) specific receptors, and this effect is mediated by vasodilatatory prostaglandins. At high concentrations, Ang (1-7) effects are mediated by AT1-receptors, though to a lesser extent than by Ang (1-7) specific receptors.Journal of Renin-Angiotensin-Aldosterone System 09/2005; 6(2):90-5. · 2.44 Impact Factor