Noradrenaline-induced contraction of human saphenous vein and human internal mammary artery: involvement of different alpha-adrenoceptor subtypes.
Although saphenous veins and internal mammary arteries are commonly used for coronary artery bypass grafting, only a very few comparative studies are available on alpha-adrenoceptor-mediated vasoconstriction in these vessels. Thus, we determined, in isolated rings from human saphenous vein and human internal mammary artery, contractile responses to noradrenaline (10(-8)-10(-4) M) in the absence and presence of the alpha-adrenoceptor antagonists yohimbine (alpha(2)-adrenoceptor antagonist, 10(-8)-10(-6) M), prazosin (alpha(1)-adrenoceptor antagonist, 10(-9)-10(-7) M), 5-methyl-urapidil (5-MU, alpha(1A)-adrenoceptor antagonist, 10(-8)-10(-6) M), BMY 7378 (alpha(1D)-adrenoceptor antagonist, 10(-7)-10(-6) M), and chloroethylclonidine (CEC, irreversible alpha(1B)-adrenoceptor antagonist, 3x10(-5) M for 30 min). All experiments were carried out in the presence of 10(-7) M propranolol and 10(-5) M cocaine. In both vessel types noradrenaline evoked concentration-dependent contractions. In saphenous veins yohimbine was a potent antagonist (pA(2)-value 8.32) while prazosin, 5-MU and BMY exhibited only marginal antagonistic effects. CEC, however, significantly decreased noradrenaline-induced contractions. In contrast, in internal mammary arteries prazosin (pA(2)-value 9.65) and 5-MU (pK(B)-values 7.2-7.5) were potent antagonists, while yohimbine and BMY exhibited only weak antagonistic effects. CEC, however, significantly decreased noradrenaline-induced contractions. We conclude that in saphenous vein the contractile response to noradrenaline is mediated predominantly by alpha(2)-adrenoceptors, while in internal mammary artery it is mediated (to a major part) by alpha(1B)- and (to a minor part) by alpha(1A)-adrenoceptors.
Giessler
Christine
C
Institute of Pharmacology, University of Halle, Magdeburger Strasse 4, Germany.
Wangemann
Thekla
T
Silber
Rolf-Edgar
RE
Dhein
Stefan
S
Brodde
Otto-Erich
OE
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000368:Aged; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification* / Q000378:metabolism / Q000502:physiology; D012044:Regression Analysis; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; C057446:5-methylurapidil; D015016:Yohimbine; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin