Angiotensin-(1–7) Augments Bradykinin-Induced Vasodilation by Competing With ACE and Releasing Nitric Oxide

Abstract

The response was specific for BK, Since Ang-( l-7) did not augment the vasoddatlon induced by elther acetylchohne (0 05 pmol/L) or sodium mtroprusside (0 1 pmol/L) Moreover, neither angiotensm

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

“…Moreover, Ang-(1-7) potentiated the vasodilatory effect of bradykinin administered to conscious rats, and this response was significantly attenuated by indomethacin, suggesting the involvement of prostaglandins (Paula et al 1995). This effect was later confirmed by us, and we showed that this effect of Ang-(1-7) to potentiate bradykinin-induced vasodilation was due to the ability of Ang-(1-7) to inhibit ACE activity and release NO (Li et al 1997), thereby decreasing the metabolism of bradykinin and further stimulating vasodilation. More recently, mas receptor activation by Ang-(1-7) improved endothelial function (Faria-Silva et al 2005).…”

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

“…Endothelial cells are not only involved in the production but also in the metabolism of this heptapeptide (Velez et al 2012). The ACE2/Ang-(1-7)/Mas axis induces the release of vasodilators, including prostanoids, NO and endothelium-derived hyperpolarizing factor (Porsti et al 1994, Brosnihan et al 1996, Li et al 1997, Muthalif et al 1998, Iyer et al 2000, Fernandes et al 2001, Heitsch et al 2001. Accordingly, Ang-(1-7) elicits relaxation in several vascular beds (see Santos et al (2000) for review).…”

“…This BK-potentiating effect of Ang-(1-7) may contribute for its cardiovascular effects in normotensive (Paula et al 1995, Oliveira et al 1999, Greco et al 2006 and hypertensive (Lima et al 1997, Fernandes et al 2001 rats. Several mechanisms have been proposed to explain the BK-potentiating activity of Ang-(1-7), including ACE inhibition since Ang-(1-7) is an ACE substrate (Li et al 1997, Tom et al 2001, allosteric changes in ACE (Erdos et al 2002), and Mas-mediated changes in the BK signaling (Paula et al 1995, Oliveira et al 1999, Fernandes et al 2001, Ferreira et al 2001. In addition, vascular Ang-(1-7) actions could involve modulation of vascular effects of Ang II (Roks et al 1999, Stegbauer et al 2004.…”

Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7)

“…In the spontaneously hypertensive rat (SHR), the vasodilator effects of Ang-(1-7) are blocked in the presence of the cyclooxygenase 1 inhibitor, indomethacin, 25 confirming previous findings in which the vasorelaxing response of canine coronary artery ring induced by Ang-(1-7) was abolished by the BK antagonist icatibant, 26 whereas the peptide also inhibited the degradation of 125 I-[Tyr 0 ]-BK and the appearance of BK-(1-7) and BK-(1-5) metabolites in the effluent from the preparation. 27 Cross-talk between the prostaglandin-BK-nitric oxide systems and Ang-(1-7) suggests that a multilayered interaction between these systems is important for a wide array of physiological functions. 28 Similar mechanisms participate in the antiproliferative actions of Ang-(1-7) first demonstrated in vascular smooth muscle cells (VSMCs).…”