Role of alpha-1 adrenoceptor subtypes mediating constriction of the rabbitear thermoregulatory microvasculature

An acute in vivo preparation of the microvasculature of the rabbit ear was used to evaluate the functional role of alpha(1) (alpha(1))-adrenoceptor su btypes in thermoregulatory microcirculation. The effect of alpha(1)-adrenoc eptor subtype blockade on phenylephrine-induced vasoconstriction was assess ed with the alpha(1A), alpha(1B), and alpha(1D)-adrenoceptor-selective anta gonists 5-methyl-urapidil (10(-8) M), chloroethylclonidine (10(-5) M), and 8-[2-[4(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5]decane-7,9-di one dihydrochloride (BMY7378) (10(-6) M), respectively. The results demonst rated that pretreatment of the ear microvasculature with 5-methyl-urapidil or BMY7378 shifted the phenylephrine concentration-response curve rightward and significantly changed the log of the phenylephrine concentration, caus ing half-maximum stimulation (EC50) in arterioles (p < 0.05). BMY7378 shift ed the phenylephrine concentration-response curve of the arteriovenous anas tomoses about 100-fold rightward (p < 0.05). All three alpha(1)-adrenocepto r antagonists eliminated the vasoconstrictive effects of phenylephrine on v enules. The results indicate that the ear microvasculature has a heterogeno us distribution of alpha(1)-adrenoceptor subtypes. The alpha(1A) and alpha( 1D)-adrenoceptor subtypes appear to have a greater influence on constrictiv e function in arterioles, whereas the alpha(1D)-adrenoceptor is the dominan t constrictor of arteriovenous anastomoses. In general, the alpha(1)-adreno ceptor does not play a major vasoconstrictor role in venules. Chloroethylcl onidine, an irreversible alpha(1B)-adrenoceptor antagonist, induced contrac tile responses in the ear microvasculature, probably due to its alpha(2)-ad renoceptor agonist effects. This study extended our understanding of the ad renergic receptor control mechanisms of a cutaneous thermoregulatory end or gan characterized by two parallel perfusion circuits providing nutritional and thermoregulatory functions.