Adrenoceptor-stimulated endothelium-dependent relaxation in porcine intrapulmonary arteries

The responses of rings of isolated adult porcine intrapulmonary arteries to noradrenaline were observed. The effects of prazosin (alpha-1 adrenoceptor antagonist), yohimbine (alpha-2 adrenoceptor agonist) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the noradrenaline responses were studied. In addition, following contraction with prostaglandin PGF2 alpha, the responses to noradrenaline or UK 14304 (alpha-2 adrenoceptor agonist) were observed alone and in the presence of either prazosin or yohimbine. The effects of UK14304 were also observed following precontraction with phenylephrine. Noradrenaline produced an initial increase in vascular tone followed by a decrease and then a second increase in tone at high concentrations. The initial contractile response was inhibited by prazosin or yohimbine. L-NAME or endothelium removal enhanced the contractile responses and abolished the mid range reduction in tone. Following PGF2 alpha pre-contraction, UK14304 further increased the tone, with a reduction in tone at higher concentrations. the contractile effect was augmented by prazosin. Following phenylephrine pre-contraction, UK14304 only produced reduction in tone. In conclusion, in porcine intrapulmonary arteries, L-NAME inhibited noradrenaline induced endothelium dependent reduction in tone, which was also inhibited by alpha-1 and alpha-2 antagonists. UK14304 demonstrated partial alpha-1 agonism.