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
Tm. Zellers et al., 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, ACT PHAR SI, 21(2), 2000, pp. 131-138
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.