title: Hydrogen peroxide generated from cardiac myocytes impacts metabolic dilation in coronary arterioles.
abstract: 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.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Fukushima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otake
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
mesh_terms: 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*
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide