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Effect of chronic inhibition of nitric oxide synthase on ocular blood flow and glucose metabolism in the rat
  1. Colm O’Briena,
  2. Paul A T Kellyb,
  3. Isobel M Ritchieb
  1. aDepartment of Ophthalmology, University of Edinburgh, Scotland , bDepartment of Clinical Neurosciences, University of Edinburgh, Scotland
  1. Dr Colm O’Brien, Princess Alexandra Eye Pavilion, Chalmer’s Street, Edinburgh EH3 9HA.

Abstract

AIMS To investigate the effects of chronic administration of nitric oxide synthase inhibition on ocular blood flow and metabolic demand in the rat and to compare these effects with changes in the cerebral and peripheral circulation.

METHODS Male Sprague-Dawley rats were injected with the nitric oxide synthase inhibitor L-NAME (75 mg/kg ip), either on a single occasion only or once daily for 10 consecutive days. Controls were injected with saline. Regional blood flow and glucose metabolism were measured from tissue samples, using [14C]-iodoantipyrine and [14C]-2-deoxyglucose respectively, 1 hour after either acute L-NAME injection or 1 hour after the last injection of the chronic treatment protocol.

RESULTS Mean arterial pressure was significantly increased (+31%) following the acute injection (indicating peripheral vasoconstriction) and this effect was enhanced (+50%) following chronic treatment. In both the ocular and cerebral circulation, blood flow was decreased following acute treatment (−48% and −43% respectively). However, while this response was totally attenuated in the cerebral circulation following chronic L-NAME treatment (−4%), the ocular circulation remained responsive (−57%). Metabolic demand in brain and eye tissue, as reflected in the accumulation of 2-deoxyglucose, was unaffected by either acute or chronic treatment with L-NAME.

CONCLUSION Homeostatic mechanisms appear to be activated in the cerebral circulation which re-establish flow metabolism homeostasis, and the effect of L-NAME on cerebral blood flow is attenuated following repeated exposure. This process does not seem to happen in the ocular circulation and, thus, the ocular vasculature appears to behave more like those blood vessels which determine total peripheral resistance than the cerebral circulation. It remains to be seen whether the sustained decrease in blood flow in the eye is sufficient to compromise ocular function and render the eye susceptible to damage from chronic L-NAME induced oligaemia.

  • nitric oxide
  • ocular blood flow
  • glucose utilisation

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