alpha-Methylnoradrenaline-induced contractions in rat aorta are mediated via alpha 1D-adrenoceptors.
The subtype(t) of alpha-adrenoceptor-mediating contractions to alpha-methynoradrenaline in the rat aorta has been investigated by using alpha-adrenoceptor-selective competitive antagonists and the alpha 1-adrenoceptor selective agonist, phenylephrine, for comparison. alpha-Methylnoradrenaline and phenylephrine elicited concentration-dependent contractions in the endothelium-denuded and endothelium-intact aortic rings with similar potencies and maximal effects. alpha-Methylnoradrenaline- and phenylephrine-induced contractions in endothelium-denuded aortic rings were competitively antagonized by prazosin (pA2 = 9.38 and 9.13; respectively) and rauwolscine (pA2 = 7.19 and 6.60, respectively). This confirms that there is an alpha 1- and a non alpha 2-adrenoceptor response to alpha-methylnoradrenaline in the rat aorta. The subtype selective alpha 1D-adrenoceptor antagonist, BMY 7378, was found to antagonize contractions to alpha-methylnoradrenaline and phenylephrine competitively in endothelium-denuded and endothelium-intact aortic rings. The pA2 values of BMY 7378 against alpha-methylnoradrenaline (8.39 and 8.41; endothelium-intact and endothelium-denuded, respectively) and phenylephrine (8.64 and 8.76; endothelium-intact and endothelium-denuded, respectively), are consistent with its published functional potency and clonal alpha 1D-adrenoceptor binding affinity. In addition, contractions to alpha-methylnoradrenaline and phenylephrine in endothelium-denuded aortic rings, were potently inhibited by WB 4101 with pA2 values of 9.75 and 9.25, respectively. The high pA2 values for WB 4101 indicate that the alpha 1B-adrenoceptor subtype does not seem to participate in alpha-methylnoradrenaline (and phenylephrine) induced contractions in this artery. These results suggest that the alpha 1D-subtype plays a determining role in rat aorta contractions induced by alpha-methylnoradrenaline.
Castillo
E F
EF
Departamento de Fisiología y Farmacología de la Escuela Superior de Medicina, Mexico.
Valencia
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I
Bobadilla
R M
RM
Villalon
C M
CM
Castillo
C
C
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D008771:Nordefrin / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D008771:Nordefrin