NITRIC-OXIDE IN RETINAL AND CHOROIDAL BLOOD-FLOW AUTOREGULATION IN NEWBORN PIGS - INTERACTIONS WITH PROSTAGLANDINS

The role of nitric oxide (NO) as well as its interaction with prostagl andins (PG) in setting the limits of autoregulation of retinal blood f low (RBF) and choroidal blood flow (ChBF) were studied in newborn pigs (1-5 d old). Blood hows were measured by the microsphere technique. L ow and high ocular perfusion pressures (OPP) were induced by inflating balloon-tipped catheters placed at the aortic root and isthmus, respe ctively. Animals were treated with the NO synthase inhibitors, N-G-nit ro-L-arginine methyl ester (L-NAME, 1 mg/kg followed by 50 mu g/kg/min ; n = 12) or N-G-monomethyl-L-arginine (L-NMMA, same dose as L-NAME; n = 3), or with saline (n = 12). In separate animals (n = 42), guanosin e 3',5'-cyclic monophosphate (cGMP), the second messenger for NO, and PG were measured at an average OPP of 90 mm Hg and 125 +/- 6 mm Hg; cG MP levels served as an index of NO release. The effect of the NO donor sodium nitroprusside on choroidal vessel diameter was determined usin g video imaging of isolated eyecup preparations. In control animals RB F was constant only within a range of 30 to 80 mm Hg OPP (r = 0.03, p > 0.9). There was no autoregulation of ChBF which increased as a funct ion of OPP (tau = 0.58-0.72, p < 0.01). L-NAME and L-NMMA prevented a change in RBF and ChBF from 30 to 146 mm Hg [the highest OPP studied ( r < 0.3, p > 0.15)] and caused an increase in retinal as well as choro idal vascular resistance as OPP was raised; these agents did not affec t ocular blood flow at OPP < 30 mm Hg. Elevated OPP caused increases i n cGMP, 6-keto-PGF(1 alpha), and PGE(2) in the choroid (a vascular tis sue), which were prevented by L-NAME and L-NMMA. Sodium nitroprusside caused a dilatation of choroidal vessels in isolated eyecup preparatio ns, which was significantly attenuated by indomethacin. Data suggest a role for NO in the autoregulation of RBF and ChBF in the newborn such that a release of NO during a rise in OPP prevents adequate constrict ion necessary for maintaining RBF and ChBF constant; data also suggest that the vasodilator effect of NO might in part be mediated through a release of PG.