Prostacyclin-induced relaxations of small porcine pulmonary arteries are enhanced by the basal release of endothelium-derived nitric oxide through an effect on cyclic GMP-inhibited-cyclic AMP phosphodiesterase.
OBJECTIVE
To study the interactions between prostacyclin and endothelium-derived nitric oxide in porcine pulmonary arteries.


METHODS
Rings of 5th 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 phenylephrine contraction) that were inhibited by the inhibitors of the L-arginine nitric oxide pathway, oxyhemoglobin and N omega-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach 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 prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin-induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium.


CONCLUSIONS
These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by basally released endothelium-derived nitric oxide.
Department of Pediatrics, Division of Cardiology University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard, Dallas, TX 75235, USA. tzellers@childmed.dallas.tx.us
T M
TM
Zellers
Y Q
YQ
Wu
J
J
McCormick
P M
PM
Vanhoutte
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects; D013556:Swine, Miniature; D014664:Vasodilation / Q000187:drug effects*
C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D011464:Epoprostenol; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP