Alterations of beta-adrenoceptor mediated relaxations of atherosclerotic human coronary arteries.
Preliminary investigations suggest that atherosclerosis attenuates the beta-adrenergic relaxations of human coronary arteries. However, this finding could not be related specifically to the beta-agonists and responses to non-adrenergic relaxants could be also decreased. Therefore segments of coronary arteries were isolated from 35 human hearts (aged 18-58 years) with various degrees of atherosclerosis. On rings precontracted with KCl (15 mM) concentration-response curves were constructed for isoproterenol and were compared with the responses to three other vasodilators: forskolin, nitroglycerin and SIN1 (the active metabolite of molsidomine). At the end of each experiment, the degree of atherosclerosis was scored by histological examination. Moderate (class II) and severe (class III) lesions of atherosclerosis significantly altered the maximal response to isoproterenol, which was decreased from 76 +/- 5% (of KCl-induced contraction) to 33 +/- 6% in class II and 22 +/- 5% in class III. Conversely, the maximal relaxations to forskolin, nitroglycerin and SIN1 were not significantly modified. However, in class III, there was a significant shift to the right of the dose-response curves to nitroglycerin and SIN1 (but not to forskolin). Thus our results show that atherosclerosis markedly attenuates the relaxations of human coronary smooth muscles to isoproterenol, and that this abnormality is not related to an alteration in the intrinsic capacity of the atherosclerotic vessel to relax.
Berkenboom
G
G
Cardiology Department, Erasmus Hospital, Brussels, Belgium.
Fontaine
J
J
Degre
S
S
D000328:Adult; D005576:Colforsin / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D008981:Molsidomine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D011189:Potassium Chloride; D008981:Molsidomine; D005996:Nitroglycerin