The influence of atherosclerosis on the mechanical responses of human isolated coronary arteries to substance P, isoprenaline and noradrenaline.
1 The responses to substance P, isoprenaline and noradrenaline were observed on human isolated coronary arteries removed from 30 human hearts, and were classified according to the age of the hearts, the presence or absence of cardiac failure and the degree of atherosclerosis. 2 The endothelium-dependent vasodilator, substance P (0.1 microM), relaxed rings precontracted with prostaglandin F2 alpha, (PGF2 alpha, 1 microM) when they were devoid of atherosclerosis. The presence of moderate or severe lesions of atherosclerosis abolished this response. There was no difference in the response, related to either the age of the hearts or to the presence or absence of cardiac failure. 3 The dose-response curves to isoprenaline (an endothelium-independent vasodilator) were also markedly altered by the presence of atherosclerotic lesions, while aging and the presence of cardiac failure did not alter the maximal relaxation. These last 2 factors induced only a rightward shift of the dose-response curves. 4 On severely atherosclerotic rings, beta-adrenoceptor-mediated responses were so altered that the effect of noradrenaline was wholly vasoconstrictor (via alpha-adrenoceptors). This response was not modified after pretreatment with atenolol (10 microM). 5 It is concluded that atherosclerosis in human coronary arteries, induces alterations in the responses to substance P and to beta-adrenoceptor agonists. The beta-adrenoceptor-mediated relaxations seem more influenced by the presence of atherosclerosis than they are by aging or by the down-regulation induced by cardiac failure. Conversely, the alpha-adrenoceptor responses appear to be well preserved.
D000293:Adolescent; D000328:Adult; D001161:Arteriosclerosis / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D013373:Substance P; D011189:Potassium Chloride; D007545:Isoproterenol; D009638:Norepinephrine