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Cardiovascular Research 1991 25(12):1002-1009; doi:10.1093/cvr/25.12.1002
© 1991 by European Society of Cardiology
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Copyright © 1991, European Society of Cardiology

Age related attenuation of the endothelium dependent relaxation to noradrenaline in isolated pig coronary arteries

Toyoaki Murohara, Hirofumi Yasue, Masamichi Ohgushi, Naritsugu Sakaino and Michihisa Jougasaki

Division of Cardiology, Kumamoto University Medical School, 1-1-1 Honjo, Kumamoto 860, Japan

Correspondence to: Dr Yasue

Study objective — The aim was to investigate the relationship between vascular aging and endothelial regulation of the vascular tone by various agonists in isolated pig coronary arteries.

Experimental materials and design — Coronary artery rings from young (4-6 month old) and aged (3-4 years old) Yorkshire pigs were studied under isometric tension by organ chamber experiments. Cumulative concentration-response curves were obtained for vasorelaxing agents including noradrenaline (with β blocker), substance P, bradykinin, and glyceryl trinitrate in rings precontracted with prostaglandin F2{alpha} (PGF2{alpha}). The degree of atherosclerosis of the coronary arteries was examined by light microscopy after the pharmacological experiments.

Measurements and main results — In the presence of propranolol (3 x 10–6M), noradrenaline (10–8–10–5 M) caused endothelium dependent relaxation. The maximum relaxation was significantly greater in the young [45.4(SEM 2.5)% of the magnitude of precontraction induced by PGF2{alpha}] than in the aged group [26.9(3.0)%] (p<0.001). However, magnitudes of relaxation to substance P, bradykinin, and glyceryl trinitrate were not significantly different between the young and the aged groups. The {alpha}2 antagonist yohimbine (3 x 10–6M) inhibited the endothelium dependent relaxation to noradrenaline, but the oil antagonist prazosin (10–6M) failed to inhibit the response. Gossypol (3 x 10–5M) and methylene blue (10–5M), both inhibitors of endothelium dependent relaxation, abolished {alpha}2 adrenoceptor mediated relaxation, but a cyclo-oxygenase inhibitor indomethacin (10–5M) did not affect the response. Histologically almost all young pig coronary arteries were free of atherosclerotic changes, whereas aged arteries had fatty streaks with slightly narrowed lumen in 22 of 38 rings (58%). The remaining aged pig coronary rings were free from atherosclerosis. Comparison of the endothelium dependent relaxation to noradrenaline between the rings with fatty streaks and those without lesions in the aged pigs suggested that the attenuated response was due both to vascular aging and to fatty streak development.

Conclusions — The endothelium dependent relaxation to noradrenaline via the {alpha}2 adrenoceptor was attenuated by vascular aging and also by fatty streak formation in isolated pig coronary arteries. Thus vascular aging may affect the sympathetic regulation of the coronary arterial tone by the attenuation of endothelium dependent relaxation to catecholamines via {alpha}2 adrenoceptors.

KEYWORDS endothelium dependent relaxation; EDRF; noradrenaline; {alpha}2 adrenergic receptor; isolated pig coronary artery; aging; early atherosclerosis; coronary spasm


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