Hydrogen peroxide generated from cardiac myocytes impacts metabolic dilation in coronary arterioles.
During oxidative cardiac metabolism, the myocardium produces reactive oxygen species, such as superoxide and hydrogen peroxide (H(2)O(2)). We hypothesized H(2)O(2) is a coronary metabolic dilator linking regulation of coronary tone with myocardium metabolism. Dilation of isolated, pressurized coronary arterioles (76 +/- 10 microm, 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)]. H(2)O(2) was significantly generated by pacing (400 bpm n = 11, 9.3 +/- 0.4 microM P < 0.01, versus unpaced) and the addition of this supernatant caused vasodilation (500 microL 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 H(2)O(2), myocytes were also stimulated at 400 bpm following treatment with Mn-TBAP (25 microM), which mimics the action of Mn-SOD, and apocynin (3 mM), an NADPH oxidase inhibitor (n = 11, each). Mn-TBAP increased H(2)O(2) generation in myocyte supernatant stimulated at 400 bpm (12.2 +/- 0.8 microM, 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 H(2)O(2). We conclude that H(2)O(2) is a key metabolic vasodilator produced by myocardium.
Otake
Atsushi
A
Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Fukushima, Japan.
Saitoh
Shu-ichi
S
Takeishi
Yasuchika
Y
D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D018929:Cell Culture Techniques; D003326:Coronary Circulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D016877:Oxidants; D006861:Hydrogen Peroxide