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This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/H226    most recent 00480.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yamaguchi, O. Articles by Takeishi, Y. Search for Related Content PubMed PubMed Citation Articles by Yamaguchi, O. Articles by Takeishi, Y.

Regulation of coronary vascular tone via redox modulation in the ₁-adrenergic-angiotensin-endothelin axis of the myocardium

¹First Department of Internal Medicine, Fukushima Medical University, Fukushima; and ²Cardiology Center, Hoshi General Hospital, Koriyama, Japan

Submitted 7 May 2008 ; accepted in final form 6 November 2008

We hypothesized that ₁-adrenoceptor stimulation of cardiac myocytes results in the production of an endothelin (ET)-releasing factor that stimulates the coronary vasculature to release ET and, by manipulating the redox state of cardiac and vascular cells, may influence the extent of ₁-adrenergic-ET-1 vasoconstriction. Dihydroethidium (DHE) and dichlorodihydrofluorescein (DCF) intensities were increased by phenylephrine stimulation in isolated rat cardiac myocytes, which were enhanced by the mitochondrial electron transport chain complex I inhibitor rotenone (DHE: 20.4 ± 1.2-fold and DCF: 25.2 ± 0.9-fold, n = 8, P < 0.01, respectively) but not by the NADPH oxidase inhibitor apocynin. Olmesartan, an angiotensin II type 1 receptor antagonist, and enalaprilate did not change DHE and DCF intensities by phenylephrine. Next, we measured the vasoconstriction of isolated, pressurized rat coronary arterioles (diameter: 74 ± 8 µm) in response to supernatant collected from isolated cardiac myocytes. The addition of supernatant from phenylephrine-stimulated myocytes to a 2-ml vessel bath (n = 8 each) caused volume-dependent vasoconstriction (500 µl: –14.8 ± 2.2%). Olmesartan and TA0201, an ET type A receptor antagonist, converted vasoconstriction into vasodilation (8.5 ± 1.2% and 10.5 ± 0.5%, P < 0.01, respectively) in response to supernatant from phenylephrine-stimulated myocytes, which was eliminated with catalase. Vasoconstriction was weakened using supernatant from phenylephrine with rotenone-treated myocytes. Treatment of arterioles with apocynin to myocyte supernatant converted vasoconstriction into vasodilation (7.8 ± 0.8%, P < 0.01). These results suggest that ₁-adrenergic stimulation in cardiac myocytes produces angiotensin I and H₂O₂ and that angiotensin releases ET-1 through NADPH oxidase in coronary arterioles. Thus, coronary vasoconstriction via the -adrenergic-angiotensin-ET axis appears to require redox-mediated signaling in cardiac and vascular cells.

₁-adrenoceptor; coronary vasomotion; reactive oxygen species