CYP-epoxygenases contribute to A^sub 2A^ receptor-mediated aortic relaxation via sarcolemmal K^sub ATP^ channels

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 303; no. 10; p. R1003
• Main Authors: Ponnoth, Dovenia S, Nayeem, Mohammed A, Tilley, Stephen L, Ledent, Catherine, Mustafa, S Jamal
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 15.11.2012
• Subjects: Adenosine triphosphatase; Coronary vessels; Nitric oxide; Potassium; Rodents; Signal transduction; T cell receptors
• ISSN: 0363-6119

Previously, we have shown that ... adenosine receptor (...) mediates aortic relaxation via cytochrome P-450 (CYP)-epoxygenases. However, the signaling mechanism is not understood properly. We hypothesized that ATP-sensitive K+ (...) channels play an important role in ...-mediated relaxation. Organ bath and Western blot experiments were done using isolated aorta from ... and corresponding wild-type (WT) mice. Aortic rings from WT and ... knockout (KO) mice were precontracted with submaximal dose of phenylephrine (PE, ... M), and concentration-response curves for pinacidil, cromakalim (nonselective ... openers), and diazoxide (mitochondrial ... opener) were obtained. Diazoxide did not have any relaxation effect on PE-precontracted tissues, whereas relaxation to pinacidil (48.09 ± 5.23% in WT vs. 25.41 ± 2.73% in ...; P < 0.05) and cromakalim (51.19 ± 2.05% in WT vs. 38.50 ± 2.26% in ...; P < 0.05) was higher in WT than ... aorta. This suggested the involvement of sarcolemmal rather than mitochondrial ... channels. Endothelium removal, treatment with SCH 58651 (... antagonist; ... M), NG-nitro-l-arginine methyl ester (l-NAME, nitric oxide synthase inhibitor) and methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH, CYP-epoxygenases inhibitor; ... M) significantly reduced pinacidil-induced relaxation in WT compared with controls, whereas these treatments did not have any effect in ... aorta. Glibenclamide (... channel inhibitor, ... M) blocked 2-p-(2-carboxyethyl)phenethylamino-5'N-ethylcarboxamido adenosine hydrochloride (CGS 21680, ... agonist)-induced relaxation in WT and changed 5'-N-ethylcarboxamide (NECA) (nonselective adenosine analog)-induced response to higher contraction in WT and ... 5-Hydroxydecanoate (5-HD, mitochondrial ... channel inhibitor, ... M) had no effect on CGS 21680-mediated response in WT aorta. Our data suggest that ...-mediated vasorelaxation occurs through opening of sarcolemmal ... channels via CYP-epoxygenases and possibly, nitric oxide, contributing to pinacidil-induced responses. (ProQuest: ... denotes formulae/symbols omitted.)