Angiotensin-(1-7) and low-dose angiotensin II infusion reverse salt-induced endothelial dysfunction via different mechanisms in rat middle cerebral arteries

Abstract

The goals of this study were to 1) determine the acute effect of ANG-(1-7) on vascular tone in isolated middle cerebral arteries (MCAs) from Sprague-Dawley rats fed a normal salt (NS; 0.4% NaCl) diet, 2) evaluate the ability of chronic intravenous infusion of ANG-(1-7) (4 ng·kg(-1)·min(-1)) for 3 days to restore endothelium-dependent dilation to acetylcholine (ACh) in rats fed a high-salt (HS; 4% NaCl) diet, and 3) determine whether the amelioration of endothelial dysfunction by ANG-(1-7) infusion in rats fed a HS diet is different from the protective effect of low-dose ANG II infusion in salt-fed rats. MCAs from rats fed a NS diet dilated in response to exogenous ANG-(1-7) (10(-10)-10(-5) M). Chronic ANG-(1-7) infusion significantly reduced vascular superoxide levels and restored the nitric oxide-dependent dilation to ACh (10(-10)-10(-5) M) that was lost in MCAs of rats fed a HS diet. Acute vasodilation to ANG-(1-7) and the restoration of ACh-induced dilation by chronic ANG-(1-7) infusion in rats fed a HS diet were blocked by the Mas receptor antagonist [D-ALA(7)]-ANG-(1-7) or the ANG II type 2 receptor antagonist PD-123319 and unaffected by ANG II type 1 receptor blockade with losartan. The restoration of ACh-induced dilation in MCAs of HS-fed rats by chronic intravenous infusion of ANG II (5 ng·kg(-1)·min(-1)) was blocked by losartan and unaffected by d-ALA. These findings demonstrate that circulating ANG-(1-7), working via the Mas receptor, restores endothelium-dependent vasodilation in cerebral resistance arteries of animals fed a HS diet via mechanisms distinct from those activated by low-dose ANG II infusion.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…However, in C57Bl/6 mice, MAS knockout does not alter blood pressure ). Short-term Ang(1-7) infusion in normotensive rats enhanced endothelial function (Faria-Silva et al, 2005), which may be also be conserved in other species (Langeveld et al, 2008;Durand et al, 2010;Beyer et al, 2013;Jarajapu et al, 2013;Tassone et al, 2013).…”

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

“…In the FVB/N mouse background, the endothelial dysfunction is associated with an increase in blood pressure , whereas in C57Bl/6 mice, no alteration of blood pressure was observed . The endothelial dysfunction associated with Mas deficiency in two genetic backgrounds is in Mas-Related Genes keeping with the improvement of endothelial function produced by short-term Ang-(1-7) infusion in normotensive rats (Faria-Silva et al, 2005) and with the improvement of Mas-mediated vascular function in many species and conditions (Langeveld et al, 2008;Durand et al, 2010;Stegbauer et al, 2011;Beyer et al, 2013;Jarajapu et al, 2013;Tassone et al, 2013).…”

Angiotensin-(1–7) Modulates Angiotensin II-Induced Vasoconstriction in Human Mammary Artery

“…As previously referred, ANG-(1-7) exerts important vasodilator effects in various experimental animal vascular territories, mainly in rat, including aorta [33], renal arteries [34], mesenteric arteries [35] and cerebral arteries [36]. Moreover, a clear benefit of this heptapeptide has been observed in animal models of hypertension through modulation of vascular resistance but also due to relevant effects on kidney, heart and autonomic nervous system [37,38].…”