INCREASED NITRIC-OXIDE SYNTHESIS AND ACTION PRECLUDE CHOROIDAL VASOCONSTRICTION TO HYPEROXIA IN NEWBORN PIGS

We tested the hypothesis that hyperoxia does not cause adequate constr iction of choroidal vessels of the newborn (1 to 5 days old) pig, resu lting in increased O-2 delivery to the retina, possibly due to excess production and/or effects of vasodilators such as nitric oxide (NO). H yperoxia (100% O-2, 45 minutes) led to a decrease in retinal blood flo w (RBF) of both newborn and juvenile (5 to 6 weeks old) pigs and also reduced choroidal blood flow (ChBF) in juvenile but not in newborn pig s; the absence of hyperoxia-induced ChBF response in the newborn was a ssociated with a rise in choroidal O-2 delivery. Ibuprofen (prostaglan din G/H synthase inhibitor) and 1,3-dimethyl-2-thiourea (a free radica l scavenger) did not modify the choroidal hemodynamic responses to hyp eroxia in newborn pigs. However, in newborn animals treated with the N O synthase (NOS) inhibitor N-G-nitro-L-arginine methyl eater (L-NAME), hyperoxia caused a decrease in blood flow and O-2 delivery to the cho roid. Consistent with these effects of L-NAME, hyperoxia induced an in crease in choroidal cGMP in newborn pigs ventilated with 100% O-2 and stimulated nitrite production in isolated choroids exposed to hyperoxi a from newborn but not juvenile pigs; these effects were inhibited by NOS blockers. Also, both constitutive and inducible NOS activities wer e higher in choroidal tissues from newborn than from juvenile animals. In addition, the vasorelaxant effect of the NO donor sodium nitroprus side in vitro was also greater on choroids from newborn than from juve nile pigs. Finally, L-NAME prevented the hyperoxia-induced increase in peroxidation products in the choroid of newborns. It is concluded tha t hyperoxia does not lead to a decrease in blood flow and O-2 delivery to the choroid of the newborn because of increased NO synthesis and e ffects; since the choroid is the main source of O-2 supply to the reti na, the present data contribute in providing an explanation for the in creased susceptibility of the immature neonate to hyperoxia-induced re tinopathy.