FUNCTIONAL DISTRIBUTION AND ROLE OF ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE MESENTERIC VASCULATURE OF THE RAT

Because alpha-1 adrenoceptor subtypes are distributed differentially i n different arteries, experiments were conducted to determine the func tional contribution of these subtypes in conduit vs, resistance vessel s. Concentration- or dose-response curves for norepinephrine were obta ined from aortic rings, superior mesenteric artery rings or the isolat ed perfused mesenteric vasculature from male Sprague-Dawley rats. Freq uency-response curves to transmural electrical stimulation were obtain ed from the latter two preparations. The effects of and methylurapidil (5-MU), an alpha-1a adrenoceptor antagonist, and chloroethylclonidine (CEC), an alpha-1b adrenoceptor antagonist, on contractile responses were determined. In artery rings, 5-MU (30 nM) had no effect on the EC (50) Of norepinephrine but reduced the maximum response of the mesente ric artery rings by nearly 25%. In the perfused mesenteric vasculature , however, 5-MU (30 nM) shifted the ED(50) for norepinephrine about 40 -fold while reducing the maximum response by 30%. 5-MU depressed the f requency-response curve in the perfused mesenteric vasculature by near ly 80%, but did not alter the response of artery rings. In aorta, pret reatment with CEC (10 mu M) shifted the concentration-response curve o f norepinephrine by 800-fold without effecting the maximum. In mesente ric artery rings and perfused mesenteric vasculature, CEC reduced the slope and maximum response of both frequency-response and norepinephri ne dose-response curves. Responses to norepinephrine (10 mu M) in the perfused mesentery were abolished by 5-MU and reduced only 25% by nife dipine. These data suggest that the density or role of alpha-1a adreno ceptors may be greater in resistance Vessels than in conduit vessels.