Role of Nitric Oxide and Endothelium in Rat Pial Vessel Dilation Response to Isoflurane

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Abstract
Er were measured using intravital microscopy. The cerebral microvascular dilatory response was recorded as percent change of diameter from baseline. The pial vessels were suffused with sodium nitroprusside (SNP) or S-nitroso-acetyl-peni-cillamine (SNAP) to verify intact vascular smooth muscle relaxation function, and with adenosine diphosphate (ADP) and/or acetylcholine (ACh) to verify endothelial NO-generating capability. To isolate NO's role in the cerebral microvascular effects of isoflurane (Protocol I), microvessels were studied with and without nitric oxide synthase (NOS) inhibition by topically applied nitro-l-arginine methyl ester (l-NAME). In controls, l-NAME was replaced by its inactive enantiomer, nitro-d-arginine methyl ester (d-NAME). Mercury light plus fluorescein dye (LD) endothelial injury (Protocol II) was used to delineate an endothelium-mediated mechanism. Subsequently, vasodilator applications were repeated to verify the desired effects of the interventions and followed by suffusion of isoflurane 1%, 2%, and 3% (Protocol I) or isoflurane 3% (Protocol II). Suffusions of SNP, ADP, and ACh induced diameter increases of 15%-30%. NOS inhibition with l-NAME greatly attenuated ADP and ACh responses, but did not alter the SNP response, confirming that NO generation was blocked, but not NO action. These responses were unaffected in d-NAME-suffused rats. Isoflurane dilated arterioles 17% and venules 6% in the presence of d-NAME suffusion. However, after NOS inhibition with l-NAME, the application of isoflurane caused vasoconstriction rather than dilation. Applications of SNAP and ACh significantly increased pial arteriolar diameters. ld endothelial injury, versus dye only, significantly attenuated the ACh response but did not change the SNAP response. The isoflurane response (12% dilation) was converted to a 5% vasoconstriction. In summary, isoflurane causes cerebral microvascular dilation in vivo. NO synthesis and endothelium are essential components in this response. Address correspondence and reprint requests to Heidi M. Koenig, MD, Department of Anesthesiology, 3 Kaplan, Michael Reese Hospital/University of Illinois-Chicago, 2929 South Ellis, Chicago, IL 60616. This work was supported in part by a Fiscal Year 1994 Grant from Michael Reese Hospital and Foundation. Accepted for publication June 10, 1994. © 1994 International Anesthesia Research Society...

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