Aging impairs myocardium-induced dilation in coronary arterioles: role of hydrogen peroxide and angiotensin.
The mechanisms that drive age-related modifications of coronary circulation by myocardium have not been fully defined. To elucidate the aging effect on myocyte-induced vascular response, we measured changes in the diameter of isolated coronary arterioles to supernatant collected from isolated cardiac myocytes of young (2 mo) and old (24 mo) rats (stimulated at 400 beats/min, n=10, each). The H(2)O(2) level in pacing myocyte supernatant was greater in old rats than in young ones (15.9±1.8 vs. 9.5±0.7μM, P<0.01). Catalase activity in myocytes decreased 38.6±5.2% in old rats compared to that in young rats. Vasodilation with young-myocyte supernatant (M) (response to 500μl; young-arterioles (A) 20.5±1.6%, old-A 18.2±1.2%) was more potent compared to that with old-M (young-A 10.3±0.8%, old-A 9.4±1.0%, P<0.01, respectively). Treatment with an angiotensin II receptor antagonist, olmesartan, in a vessel bath augmented vasodilation in old-M+young-A (34.9±4.0%, P<0.01) and old-M+old-A (27.2±2.8%, P<0.01). Administration of catalase converted vasodilation to vasoconstriction in old-M and eliminated vasodilation in young-M. Vascular responses with authentic H(2)O(2) and angiotensin II were similar between old- and young-A. Thus, aging increases both angiotensin and the H(2)O(2) release from myocardium. In conclusion, cardiac myocyte-dependent signaling plays an important role in determining coronary vascular tone in the aging heart.
Machii
Hirofumi
H
Department of Cardiology and Hematology, Fukushima Medical University, Hikarigaoka, Fukushima 960-1295, Japan.
Saitoh
Shu-ichi
S
Kaneshiro
Takashi
T
Takeishi
Yasuchika
Y
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D004108:Dilatation, Pathologic / Q000378:metabolism; D004452:Echocardiography; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D013481:Superoxides; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D002374:Catalase; D000109:Acetylcholine; D010100:Oxygen