Alpha-adrenoceptor stimulation of porcine pulmonary arteries.
The effects of alpha 1- and alpha 2-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 alpha 1-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 alpha 2-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 alpha 1-adrenoceptors on pulmonary arteries smooth muscle cause contraction, whilst activation of alpha 2-adrenoceptors on endothelial cells cause relaxation probably through a release of nitric oxide and a rise in cGMP.
Pepke-Zaba
J
J
Department of Respiratory Physiology, Papworth Hospital, Cambridge, UK.
Higenbottam
T W
TW
Dinh-Xuan
A T
AT
Ridden
C
C
Kealey
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin; D008729:Methoxamine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D011863:Radioimmunoassay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D000242:Cyclic AMP; D006152:Cyclic GMP; D008729:Methoxamine; D003000:Clonidine; D000109:Acetylcholine; D007213:Indomethacin