NITRIC-OXIDE DOES NOT MEDIATE AUTOREGULATION OF RETINAL BLOOD-FLOW IN NEWBORN PIG

Isoflurane-anesthetized newborn pigs were used to test the hypothesis that nitric oxide mediates autoregulatory dilations of retinal arterioles. Fundus images were monitored by videomicroscopy at x 310, and stimulus-induced changes in retinal arteriolar diameter were measured by on-line image analysis. Dilatative responses to systemic hypoxia (arterial O-2 tension 20-30 mmHg), hypotension (mean arterial blood pressure 40 mmHg), or hypercapnia (arterial CO2 tension 70-85 mmHg) were assessed after intravitreal microsuffusion of the nitric oxide synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) over the observed arterioles. Twenty-five nanomoles L-NMMA constricted arterioles by 24 +/- 2% (P < 0.01; n = 17 pigs); a significant constriction (14 +/- 2%) was still observed 80 min after drug administration (n = 5). Complete nitric oxide synthase inhibition at this dose was indicated by the findings that co-administration of 2.5 mu mol L-arginine reversed this constriction within 17 +/- 2 min (n = 3), that L-NMMA, but not D-NMMA, completely inhibited the 20 +/- 3% (P < 0.01) arteriolar dilation induced by intravitreal acetylcholine (7.5 nmol; n = 4), and that no additional constriction was evidenced after administration of a 10-fold greater concentration of L-NMMA (n = 8). However, despite the prominent arteriolar constriction induced by L-NMMA under baseline conditions, increases in retinal arteriolar diameter still occurred in response to hypoxia (n = 5), hypotension (n = 4), or hypercapnia (n = 5) in animals pretreated with 50 nmol L-NMMA; these responses did not differ significantly from arteriolar dilations observed in untreated control animals (n = 16) subjected to the same stimuli. These findings indicate that resting arteriolar tone in retina is controlled by endogenous nitric oxide biosynthesis, but autoregulatory dilatative responses to hypoxia, hypotension, and hypercapnia occur independently of nitric oxide participation.