Endothelium-derived nitric oxide synthase inhibition: Effects on cerebral blood flow, pial artery diameter, and vascular morphology in rats

Ricardo Prado, Brant D. Watson, John Kuluz, W. Dalton Dietrich

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Background and Purpose: We determined the effects of inhibiting the production of cerebral endothelium-derived nitric oxide on pial artery diameter, cortical blood flow, and vascular morphology. Methods: An inhibitor of endothelium-derived nitric oxide synthesis, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), or an equivalent volume of 0.9% saline was infused into rats intra-arterially in a retrograde fashion via the right external carotid artery at a rate of 3 mg/kg/min to a total dose of 190 mg/kg or intravenously at 1 mg/kg/min to a total dose of 15 mg/kg. Large pial arteries were continuously visualized through an operating microscope, and cortical cerebral blood flow was monitored by laser-Doppler flowmetry. To localize areas of morphological interest, the protein tracer horseradish peroxidase was injected 15 minutes before termination of the L-NAME infusion and the rats were perfusion-flxed 15 minutes later for light and electron microscopic analysis. Results: Infusion of L-NAME significantly raised arterial blood pressure at both doses (for 190 mg/kg, from 103.2±3.4 to 135±3.4 mm Hg; for 15 mg/kg, from 125±2.8 to 144.4+4.0 mm Hg). Pial arteries constricted within 10 minutes after the start of the intracarotid infusion to 40% of the preinfusion diameter, while cortical cerebral blood flow decreased to an average of 72.5% of that at baseline. Morphological abnormalities in the experimental rats included microvascular stasis and focal areas of blood-brain barrier disruption to protein. Ultrastructural examination of cortical leaky sites revealed constricted arterioles with many endothelial pinocytotic vesicles and microvilli. JH Conclusions: These observations suggest that inhibition of endothelium-derived nitric oxide synthesis affects the relation between cerebral arterial diameter and cerebral blood flow and can lead to subtle 9 cerebral vascular pathological changes consistent with focal brain ischemia.

Original languageEnglish
Pages (from-to)1118-1124
Number of pages7
JournalStroke
Volume23
Issue number8
StatePublished - Aug 1 1992

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Keywords

  • Blood-brain barrier
  • Cerebral blood flow
  • Endothelium-derived relaxing factor
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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