Abstract 10621: Senescence Marker Protein-30 Deficiency Impairs Myocardium-induced Dilation in Coronary Arterioles Associated with Reactive Oxygen Species in Aging
The underlying mechanisms that drive age-related modification of coronary circulation by myocardium have not been fully defined. Senescence marker protein-30 (SMP30) is decreased with aging, and SMP30 knock-out (KO) mouse is a useful model for aging studies. To elucidate the aging effect to coronary circulation derived by myocytes, we measured changes in diameter of isolated, pressurized coronary arterioles (28±5 µm, diameter) in wild type (WT) mice to supernatant collected from enzymatically isolated cardiac myocytes from SMP30 KO mice or WT mice (unpaced or stimulated 20 min at 500 beats/min, n=8, each). Pacing increased superoxide and hydrogen peroxide levels in cardiac myocytes. The level of hydrogen peroxide in myocytes supernatant was greater in SMP30 KO mice compared to that in WT mice (23.6±3.4 vs. 5.6±1.2 µM, P<0.01). Antimysin (2 µM), complex III inhibitor, enhanced and FCCP (1 µM), oxidative phosphorylation uncoupler in mitochondria, decreased superoxide production in both mice. Catalase or SOD activity in myocytes did not change between SMP30 KO and WT mice. The addition of supernatant (100, 200 and 500 µl) from stimulated myocytes (n=8) of SMP30 KO and WT mice caused vasodilation. However, the degree of vasodilation was smaller with SMP30 KO mice compared to that with WT mice. (responses to 500 µl supernatant, SMP30 KO mice 3.6±0.6%, WT mice 12.4±1.2%, P<0.01). Administration of catalase (5000 U) to arterioles eliminated vasodilation in response to myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in response to myocyte supernatant of SMP30 KO mice (-32.6±4.5%). This remained vasoconstriction was eliminated with olmesartan (1 mM), angiotensin II receptor antagonist, and apocynin (0.3 mM), NADPH oxidase inhibitor. Thus, SMP30 deficiency associated with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocyte. In conclusion, cardiac myocyte dependent signaling plays an important role to determine coronary vascular tone with aging.
- © 2011 by American Heart Association, Inc.