ALPHA(1)-ADRENOCEPTOR-INDUCED CONTRACTILITY IN RAT AORTA IS MEDIATED BY THE ALPHA(1D) SUBTYPE

Adrenoceptor agonists were used to characterize the alpha(1)-adrenocep tor subtype responsible for mediating tension (phasic and tonic combin ed) in the denuded rat aorta and compared with radioligand binding at alpha(1)-adrenoceptor subtypes. The rank order of potency at the rat a orta was the same as that obtained for binding affinity at the rat clo nal alpha(1d)-adrenoceptor: norepinephrine > epinephrine > cirazoline > phenylephrine > oxymetazoline > A-61603 > methoxamine. Correlation c oefficients comparing rat aortic contraction (pD(2)) to binding (pK(i) ) were 0.09-0.21 for alpha(1A/a) receptors, 0.66 for clonal alpha(1b) and 0.94 for clonal alpha(1d)-adrenoceptors. Correlation coefficients comparing the clonal alpha(1d)-adrenoceptor binding affinity to in vit ro contractile responses were 0.03 and 0.10 for the rat vas deferens a nd canine prostate alpha(1A)-adrenoceptor responses, respectively, 0.0 9 for the rat spleen alpha(1B) and as noted, 0.94 for the rat aorta. T he agreement observed between agonist potency at the rat aorta and aff inity for the alpha(1d) binding sire provide new evidence that the alp ha(1D)-adrenoceptor subtype is responsible for mediating contractions in the rat aorta.