Angiotensin-(1-7) Selectively Induces Relaxation and Modulates Endothelium-Dependent Dilation in Mesenteric Arteries of Salt-Fed Rats. J Vasc Res 2016;53(1-2):105-118
Date
10/19/2016Pubmed ID
27676088Pubmed Central ID
PMC5079160DOI
10.1159/000448714Scopus ID
2-s2.0-84989260698 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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 L-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.
Author List
Raffai G, Lombard JHMESH terms used to index this publication - Major topics in bold
AcetylcholineAngiotensin I
Angiotensin-Converting Enzyme Inhibitors
Animals
Antihypertensive Agents
Bradykinin
Dose-Response Relationship, Drug
Endothelium, Vascular
Imidazoles
In Vitro Techniques
Male
Mesenteric Arteries
Nitric Oxide
Peptide Fragments
Proto-Oncogene Proteins
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 2
Receptors, G-Protein-Coupled
Signal Transduction
Sodium Chloride, Dietary
Vasodilation
Vasodilator Agents
