Abstract 12470: Aging Impairs Myocardium-induced Dilation in Coronary Arterioles: Role of Hydrogen Peroxide and Angiotensin
The underlying mechanisms that drive age-related modification of coronary circulation by myocardium have not been fully defined. Recently, we have reported cardiac myocyte metabolites regulate coronary vascular tone. To elucidate the aging effect to coronary circulation derived by myocytes, we measured changes in diameter of isolated, pressurized coronary arterioles (56±6 μm, diameter) to supernatant collected from enzymatically isolated cardiac myocytes from young (2 mo) and old (24 mo) rats (unpaced or stimulated 20 min at 400 beats/min, n=10, each). Pacing increased superoxide and hydrogen peroxide in cardiac myocytes. The level of hydrogen peroxide in myocyte supernatant was greater in old rats compared to young rats (15.9±1.8 vs. 9.5±0.7 μM, P<0.01). Catalase activity in myocytes decreased 38.6±5.2% in old rats compared to that in young rats. The addition of supernatant (100, 200, 500 μl) from stimulated young or old rats myocytes (n=10) caused vasodilation. Vasodilation with young-myocyte supernatant (M) was more potent compared to that with old-M in both young- and old-arterioles (A) (response to 500 μl supernatant, young-M+young-A 65.4±5.6%. young-M+old-A 45.8±5.2%, old-M+young-A 29.6±3.8, old-M+old-A 16.4±1.8%, P<0.01, respectively). Treatment with angiotensin receptor antagonist, olmesartan (1 μM), in vessel bath augmented vasodilation in old-M+young-A (88.2±7.6%, P<0.01) and old-M+old-A (68.5±7.4%, P<0.01), though vessel responses to young-M did not change. Administration of catalase (10000 U) to arterioles converted vasodilation to vasoconstriction in old-M (−32.6±4.4%) and eliminated vasodilation in young-M. The magnitude of dilative properties with authentic hydrogen peroxide or acetylcholine was larger in young-A than in old-A (P<0.01). Vasoconstrictive response with authentic angiotensin II did not change between old- and young-A. Thus, aging increases angiotensin and hydrogen peroxide release from cardiac myocyte. In conclusion, cardiac myocyte dependent signaling plays an important role to determine coronary vascular tone as well as decline of dilative property of arteriole in aging.
- © 2010 by American Heart Association, Inc.