Prostacyclin induced relaxations of small porcine pulmonary arteries are enhanced by the basal release of endothelium-derived nitric oxide through aneffect on cyclic GMP-inhibited-cyclic AMP phosphodiesterase

AIM: To study the interactions between prostacyclin and endothelium-derived nitric oxide in porcine pulmonary arteries. METHODS: Rings of 5(th) order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides. RESULTS: Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phe nylephrine contraction) that were Inhibited by the inhibitors of the L-argi nine nitric oxide pathway, oxyhemoglobin and N-omega-nitro-L-arginine, Thes e inhibitors did not affect the tension in rings without endothelium. Cycli c GMP-concentrations were not increased above basal concentrations in the p resence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not re ach statistical significance compared to controls. The addition of 8-bromo- cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-l-arginine (NLA), reduced the prosta cyclin-stimulated -cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinon e (a specific inhibitor of this enzyme) potentiated the prostacyclin-induce d relaxations in rings without endothelium to a magnitude similar to that o bserved in rings with endothelium. CONCLUSION: These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of p orcine pulmonary arteries is secondary to the inhibition of cyclic GMP-inhi bited cyclic AMP phosphodiesterase by basally released endothelium-derived nitric oxide.