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


RESULTS
In the presence of propranolol (3 x 10(-6)M), 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 less than 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(-6)M) inhibited the endothelium dependent relaxation to noradrenaline, but the alpha 1 antagonist prazosin (10(-6)M) failed to inhibit the response. Gossypol (3 x 10(-5)M) and methylene blue (10(-5)M), both inhibitors of endothelium dependent relaxation, abolished alpha 2 adrenoceptor mediated relaxation, but a cyclo-oxygenase inhibitor indomethacin (10(-5)M) 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.
Murohara
T
T
Division of Cardiology, Kumamoto University Medical School, Japan.
Yasue
H
H
Ohgushi
M
M
Sakaino
N
N
Jougasaki
M
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006072:Gossypol / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011433:Propranolol / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D011433:Propranolol; D006072:Gossypol; D008751:Methylene Blue; D009638:Norepinephrine; D007213:Indomethacin