Analysis of the mechanisms underlying the vasorelaxant action of angiotensin II in the isolated rat carotid

• Published in: Life sciences (1973) Vol. 78; no. 23; pp. 2676 - 2682
• Main Authors: Tirapelli, Carlos R., Fukada, Sandra Y., de Godoy, Márcio A.F., de Oliveira, Ana M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2006
• Subjects: Angiotensin II; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin-(1–7); Animals; Carotid Arteries - drug effects; Carotid Arteries - physiology; Dose-Response Relationship, Drug; Drug Antagonism; In Vitro Techniques; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Oxadiazoles - pharmacology; Peptide Fragments - pharmacology; Phenylephrine - pharmacology; Quinoxalines - pharmacology; Rat carotid; Rats; Rats, Wistar; Saralasin - pharmacology; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Vasodilation - physiology; Vasorelaxation; Angiotensin-(1–7); Angiotensin II; Vasorelaxation; Nitric oxide; Rat carotid
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.10.031

It has been suggested that low concentrations of angiotensin II cause vasoconstriction whereas high concentrations evoke vasodilation. Thus, this work aimed to functionally characterize the mechanisms underlying the relaxation induced by angiotensin II at high concentrations in isolated rat carotid rings. Experiments using standard muscle bath procedures showed that angiotensin II (0.01–3 μM) concentration dependently induces relaxation of phenylephrine-pre-contracted rings. No differences between intact or denuded endothelium were found. The angiotensin II-induced relaxation was strongly inhibited by saralasin, the non-selective antagonist of angiotensin II receptors but not by the selective antagonists of AT 1 and AT 2 receptors, losartan and PD123319, respectively. However, A-779, a selective angiotensin-(1–7) receptor antagonist, reduced the relaxation induced by angiotensin II. Administration of exogenous angiotensin-(1–7) on pre-contracted tissues produced concentration-dependent relaxation, which was also inhibited by A-779. HOE-140, the selective antagonist of the bradykinin in B 2 receptor did not produce any significant effect on angiotensin II-induced relaxation. Pre-incubation of denuded-rings with N G-nitro- l-arginine methyl ester ( l-NAME) or 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced angiotensin II-induced relaxation. On the other hand, neither indomethacin nor tetraethylammonium (TEA) produced any significant effect. The major new finding of this work is that high concentrations of angiotensin II induce relaxation of the rat carotid via activation of the NO-cGMP pathway through a mechanism that seems to be partially dependent on activation of angiotensin-(1–7) receptors.