Hydrogen Peroxide Generated From Cardiac Myocytes Impacts Metabolic Dilation in Coronary Arterioles

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During oxidative cardiac metabolism, the myocardium produces reactive oxygen species, such as superoxide and hydrogen peroxide (H2O2). We hypothesized H2O2 is a coronary metabolic dilator linking regulation of coronary tone with myocardium metabolism. Dilation of isolated, pressurized coronary arterioles (76 ± 10 μm, diameter) in reaction to supernatant collected from enzymatically isolated cardiac myocytes was measured. Isolated rat myocytes were stimulated electrically [unpaced or stimulated at 200, 400 beats/min (bpm)]. H2O2 was significantly generated by pacing (400 bpm n = 11, 9.3 ± 0.4 μM P < 0.01, versus unpaced) and the addition of this supernatant caused vasodilation (500 μL to 2 mL bath, 14.6 ± 0.7%, P < 0.01 versus unpaced). Supernatant from unpaced myocytes was not vasoactive. To clarify the source of H2O2, myocytes were also stimulated at 400 bpm following treatment with Mn-TBAP (25 μM), which mimics the action of Mn-SOD, and apocynin (3 mM), an NADPH oxidase inhibitor (n = 11, each). Mn-TBAP increased H2O2 generation in myocyte supernatant stimulated at 400 bpm (12.2 ± 0.8 μM, P < 0.01 versus 400 bpm stimulation only). Treatment of the myocytes with Mn-TBAP augmented vasodilation by the stimulated myocyte supernatant (19.6 ± 1.1%, P < 0.01 versus untreated myocyte supernatant). Apocynin did not alter vasodilation to myocyte supernatant. These results suggest that the main source of superoxide by metabolic stimuli is cardiac myocytes and Mn-SOD is a scavenger from superoxide to H2O2. We conclude that H2O2 is a key metabolic vasodilator produced by myocardium.

Hydrogen Peroxide Generated From Cardiac Myocytes Impacts Metabolic Dilation in Coronary Arterioles

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