Contractions induced by phenylephrine and noradrenaline are differently affected by endothelium-dependent relaxation...

In rings of rat aorta precontracted with phenylephrine (10 microM) or noradrenaline (10 microM), addition of carbachol (10 microM) produced an endothelium-dependent relaxation. However, regardless of the concentration of agonist tested, both the intensity and duration of the relaxation were significantly less when noradrenaline, rather than phenylephrine, was used as the precontracting agent. The different responses observed do not appear to be related to destruction of endothelium-derived relaxing factor by autoxidation of noradrenaline since neither EDTA (30 microM) nor superoxide dismutase (30 units mL-1) improved the relaxation to carbachol. In addition, in endothelium-free rings, the noradrenaline (1 microM)-induced contraction was less sensitive than the phenylephrine (1 microM)-induced contraction to sodium nitroprusside (0.1 microM) or to 8-Br-cGMP (300 microM). With phenylephrine-, but not noradrenaline-, induced contraction, the relaxation triggered by carbachol was significantly reduced by pretreatment of the aortic rings with chloroethylclonidine (50 microM), which inactivates a subpopulation of alpha 1-adrenoceptors. Thus, the results confirm that both alkylation sensitive and resistant alpha 1-adrenoceptors exist in rat aorta and indicate that EDRF may discriminate between these two alpha 1-adrenoceptor subtypes which are differently affected by phenylephrine and noradrenaline.