Abstract
The role of nitric oxide (NO) as well as its interaction with prostaglandins (PG) in setting the limits of autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) were studied in newborn pigs (1-5 d old). Blood flows were measured by the microsphere technique. Low and high ocular perfusion pressures (OPP) were induced by inflating balloon-tipped catheters placed at the aortic root and isthmus, respectively. Animals were treated with the NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg followed by 50 μg/kg/min; n = 12) or NG-monomethyl-L-arginine (L-NMMA, same dose as L-NAME;n = 3), or with saline (n = 12). In separate animals(n = 42), guanosine 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; cGMP levels served as an index of NO release. The effect of the NO donor sodium nitroprusside on choroidal vessel diameter was determined using video imaging of isolated eyecup preparations. In control animals RBF 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 function of OPP (τ = 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 choroidal vascular resistance as OPP was raised; these agents did not affect ocular blood flow at OPP < 30 mm Hg. Elevated OPP caused increases in cGMP, 6-keto-PGF1α, and PGE2 in the choroid (a vascular tissue), which were prevented by L-NAME and L-NMMA. Sodium nitroprusside caused a dilatation of choroidal vessels in isolated eyecup preparations, 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 constriction 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.
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Abbreviations
- NO:
-
nitric oxide
- RBF:
-
retinal blood flow
- ChBF:
-
choroidal blood flow
- cGMP:
-
guanosine 3′,5′-cyclic monophosphate
- PG:
-
prostaglandin
- L-NAME:
-
NG-nitro-L-arginine methyl ester
- L-NMMA:
-
NG-monomethyl-L-arginine
- ChVR:
-
choroidal vascular resistance
- OPP:
-
ocular perfusion pressure
- BP:
-
blood pressure
- IOP:
-
intraocular pressure
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Acknowledgements
The authors thank Hensy Fernandez for her technical assistance and also F. Menard Inc. (Ange-Gardien, Quebec) for their generous supply of newborn pigs.
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Supported by grants from the Medical Research Council of Canada, the American Heart Association, the Heart and Stroke Foundation of Quebec, the United Cerebral Palsy Foundation, the Hospital for Sick Children's Foundation, and the March of Dimes Birth Defects Foundation. P.H. is a recipient of a Fellowship from the Heart and Stroke Foundation of Canada.
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Hardy, P., Nuyt, A., Abran, D. et al. Nitric Oxide in Retinal and Choroidal Blood Flow Autoregulation in Newborn Pigs: Interactions with Prostaglandins. Pediatr Res 39, 487–493 (1996). https://doi.org/10.1203/00006450-199603000-00017
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DOI: https://doi.org/10.1203/00006450-199603000-00017
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