Selective alpha 1- and alpha 2-adrenoceptor agonist-induced contractions and 45Ca fluxes in the rat isolated aorta.
1 Contractile responses produced by the alpha 1-adrenoceptor selective agonist, phenylephrine, and the alpha 2-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 greater than phenylephrine greater than clonidine greater than 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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002936:Cinnarizine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D002132:Calcium Radioisotopes; D002936:Cinnarizine; D011189:Potassium Chloride; D002118:Calcium