ALPHA-ADRENOCEPTOR STIMULATION OF PORCINE PULMONARY-ARTERIES

The effects of alpha1- and alpha2-adrenoceptors stimulants on vascular tone of 188 isolated rings of pulmonary arteries from 24 pigs have been studied. The rings were pretreated with indomethacin, to inhibit cyclo-oxygenase. Isometric tension was recorded and concentrations of cyclic 3'5'-guanosine monophosphate (cGMP) and cyclic 3'5'-adenosine monophosphate (cAMP) were measured. Rings with endothelium contracted with phenylephrine (10(-5) M) (n = 41) and the alpha1-adrenoceptor agonist methoxamine (10(-3) M) (n = 24). cGMP did not change with methoxamine, but rose with phenylephrine, peaking at 30 to 45 s. This preceded the maximum rise in tension with phenylephrine which occurred later at 120 to 360 s. The alpha2-adrenoceptor agonist, clonidine (10(-5) M) (n = 33) and the muscarinic receptor agonist acetylcholine (10(-5) M) (n = 30) relaxed precontracted pulmonary arterial rings, minimum tension occurring after 120 s, whilst cGMP rose after 30-45 s. After removal of endothelium (n = 24), the tension after phenylephrine (10(-5) M) was higher and the rise in cGMP was abolished. The cAMP levels did not change with phenylephrine (10(-5) M), acetylcholine (10(-5) M), clonidine (10(-5) M) nor methoxamine (10(-3) M). Activation of alpha1-adrenoceptors on pulmonary arteries smooth muscle cause contraction, whilst activation of alpha2-adrenoceptors on endothelial cells cause relaxation probably through a release of nitric oxide and a rise in cGMP.