SELECTIVE α1‐AND α2‐ADRENOCEPTOR AGONIST‐INDUCED CONTRACTIONS AND 45Ca FLUXES IN THE RAT ISOLATED AORTA

Abstract

1 Contractile responses produced by the α₁-adrenoceptor selective agonist, phenylephrine, and the α₂-adrenoceptor selective agonists, oxymetazoline and clonidine, have been compared to those produced by noradrenaline (non selective) in the rat aorta. 2 The relative order of potency of the agonists was noradrenaline > phenylephrine > clonidine > oxymetazoline. Noradrenaline and phenylephrine produced similar maximal responses. The maximal responses produced by oxymetazoline and clonidine were about 59% and 24% respectively of those produced by noradrenaline. 3 Concentrations of agonists producing maximal contractions exhibited different response-time relationships. Responses to noradrenaline and phenylephrine were biphasic while responses induced by oxymetazoline and clonidine were monophasic. 4 In calcium-free solution, contractions stimulated by oxymetazoline and clonidine were almost abolished while those stimulated by noradrenaline and phenylephrine were reduced by about 60–70%. The calcium entry blocker, cinnarizine, almost completely inhibited responses to oxymetazoline and clonidine and reduced noradrenaline- and phenylephrine-stimulated responses by about 60%. 5 All the agonists stimulated the uptake of ⁴⁵Ca into the La³⁺-resistant Ca²⁺ fraction of the artery but only noradrenaline and phenylephrine stimulated the efflux of ⁴⁵Ca into calcium-free solution. The ⁴⁵Ca uptake stimulated by oxymetazoline and clonidine was abolished by cinnarizine and that stimulated by noradrenaline and phenylephrine was reduced by about 85%. 6 It is concluded that clonidine and oxymetazoline stimulate contractions that are totally dependent on extracellular calcium. Noradrenaline and phenylephrine stimulate contractions that are partly dependent on extracellular calcium and partly dependent on intracellular calcium stores.