We hypothesized that ₁-adrenoceptor stimulation on the cardiac myocytes results in the production of an endothelin-releasing factor, which stimulates the coronary vasculature to release endothelin, and by manipulating the redox state of cardiac and vascular cells, may influence the extent of ₁-adrenergic-endothelin-1-vasoconstriction. Dihydroethidium (DHE) and dichlorodihydrofluorescein (DCF) intensities were increased by phenylephrine stimulation in isolated rat cardiac myocytes, which was enhanced by a mitochondrial ETc-complex I inhibitor rotenone (DHE 20.4±1.2-fold, DCF 25.2±0.9-fold, n=8, P < 0.01, respectively), but not by a 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 vasoconstriction of isolated, pressurized rat coronary arteriole (74±8 µm, diameter) response to supernatant collected from isolated cardiac myocytes. 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, endothelin type-A receptor antagonist, converted vasoconstriction into vasodilation (8.5±1.2%, 10.5±0.5%, P < 0.01, respectively) in response to the 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 the myocyte supernatant converted vasoconstriction into vasodilation (7.8±0.8%, P < 0.01). These results suggest, ₁-adrenergic stimulation in cardiac myocytes produces angiotensin I and hydrogen peroxide, and angiotensin releases endothelin-1 through NADPH oxidase in coronary arterioles. Thus, coronary vasoconstriction via the -adrenergic-angiotensin-endothelin axis appears to require redox-mediated signaling in cardiac and vascular cells.