Angiotensin-(1-7) Selectively Induces Relaxation and Modulates Endothelium-Dependent Dilation in Mesenteric Arteries of Salt-Fed Rats

Abstract

This study investigated the acute effects of angiotensin-(1-7) and AVE0991 on active tone and vasodilator responses to bradykinin and acetylcholine in isolated mesenteric arteries from Sprague-Dawley rats fed a high-salt (HS; 4% NaCl) versus a normal salt (NS; 0.4% NaCl) diet. Angiotensin-(1-7) and AVE0991 elicited relaxation, and angiotensin-(1-7) unmasked vasodilator responses to bradykinin in arteries from HS-fed rats. These effects of angiotensin-(1-7) and AVE0991 were inhibited by endothelium removal, A779, PD123319, HOE140 and <smlcap>L</smlcap>-NAME. Angiotensin-(1-7) also restored the acetylcholine-induced relaxation that was suppressed by the HS diet. Vasodilator responses to bradykinin and acetylcholine in the presence of angiotensin-(1-7) were mimicked by captopril and the AT₂ receptor agonist CGP42112 in arteries from HS-fed rats. Thus, in contrast to salt-induced impairment of vascular relaxation in response to vasodilator stimuli, angiotensin-(1-7) induces endothelium-dependent and NO-mediated relaxation, unmasks bradykinin responses via activation of mas and AT₂ receptors, and restores acetylcholine-induced vasodilation in HS-fed rats. AT₂ receptor activation and angiotensin-converting enzyme (ACE) inhibition shared the ability of angiotensin-(1-7) to enhance bradykinin and acetylcholine responses in HS-fed rats. These findings suggest a therapeutic potential for mas and/or AT₂ receptor activation and ACE inhibition in restoring endothelial function impaired by elevated dietary salt intake or other pathological conditions.

Age-related changes in vascular responses to angiotensin-(1-7) in female mice

“…The vasodilation induced by Ang-(1-7) is mediated by NO production. 11 Thus, we investigated the effects of ageing on NO production in aortic rings from female mice. As shown in Figure 3 , elderly females present a significant decrease in NO as shown indirectly by DAF labelling.…”

Effect of angiotensin II and angiotensin‐(1–7) on proliferation of stem cells from human dental apical papilla

“…(1-7). A number of studies have shown the involvement of the AT2 receptor in the effects evoked by Ang-(1-7) (Bosnyak et al, 2011;Castro et al, 2005;Garcia-Garrote et al, 2019;Raffai & Lombard, 2016; Tesanovic, Vinh, Gaspari, Casley, & Widdop, 2010; Yousif et al, 2017).…”

“…However, pre‐incubation the SCAPs with PD123319, an AT2 antagonist, attenuated the proliferative effect of Ang‐(1–7). A number of studies have shown the involvement of the AT2 receptor in the effects evoked by Ang‐(1–7) (Bosnyak et al, 2011; Castro et al, 2005; Garcia‐Garrote et al, 2019; Raffai & Lombard, 2016; Tesanovic, Vinh, Gaspari, Casley, & Widdop, 2010; Yousif et al, 2017). Although Ang‐(1–7) possess lower affinity for the AT2 receptor than Ang II, this heptapeptide presents substantial selectivity for AT2 (Bosnyak et al, 2011; Jones, Vinh, McCarthy, Gaspari, & Widdop, 2008; Walters, Gaspari, & Widdop, 2005).…”

“…The heptapeptide Ang‐(1–7) is mostly formed from Ang II by the action of ACE2 (Vickers et al, 2002) and exerts its effects through activation of the Mas receptor (Santos et al, 2003). However, some studies have shown that Ang‐(1–7) is also able to activate the AT2 receptor (Castro et al, 2005; Leonhardt et al, 2017; Raffai & Lombard, 2016; Yousif, Benter, Diz, & Chappell, 2017). Generally, Ang‐(1–7) actions counteract those elicited by Ang II by activating the AT1 receptor (Cambados et al, 2017; Ferrario, Chappell, Tallant, Brosnihan, & Diz, 1997).…”

Relations of angiotensin-(1-7) with hemodynamic and cardiac structural and functional parameters in patients with hypertension and type 2 diabetes

“…According to other authors, the administration of angiotensin-(1-7) caused severe vasodilatation in patients with hypertension [16], which may indirectly indicate a deficiency of this peptide. Several experimental models show the important role of angiotensin-(1-7) in preventing systemic hypertension [17,18] and vasodilation regulation [19,20]. In rats with hypertension, induction of diabetes caused a decrease in levels of angiotensin-(1-7), and increased levels prevented cardiovascular dysfunction, which develops in hypertension with diabetes [21].…”