Chronic administration of NG‐nitro‐L‐arginine methyl ester (L‐NAME) on endothelium‐dependent relaxation of porcine brachial and femoral arteries

Endothelial derived nitric oxide contributes to endothelium‐dependent dilation in the brachial and femoral arteries of swine. The purpose of this investigation was to test the hypothesis that chronic inhibition of endothelial nitric oxide synthase (eNOS) would be compensated for by an upregulation of alternative vasodilator pathways. To test this hypothesis brachial and femoral arteries were harvested from 9 Yucatan miniature swine that were chronically administered L‐NAME (8.3 ± 0.5 mg/kg/d) in their water for 30–90 days and 11 controls. In vitro assessments of vasorelaxation to increasing doses of endothelium‐dependent [acetylcholine (ACH) and bradykinin (BK)] and –independent [sodium nitroprusside (SNP)] vasodilators were performed in the presence and absence of L‐NAME [300μM], indomethacin [5μM (INDO)], and L‐NAME + INDO in arteries from both groups. The relaxation responses of the intact and INDO arteries to both BK and ACH were significantly greater in the arteries of the control compared to the L‐NAME swine. The acute exposure of the arteries to L‐NAME and L‐NAME + INDO caused a significant reduction in relaxation response of the brachial and femoral arteries harvested from the control but not L‐NAME swine. BK induced vasorelaxation was not significantly different between the L‐NAME and control swine's brachial and femoral arteries exposed to L‐NAME and L‐NAME + INDO. These findings suggest that chronic inhibition of eNOS does not result in a compensatory upregulation of alternate vasodilator pathways within the endothelium of skeletal muscle arteries. Supported by: RR 18276, AR 048523, HL 36088, HL 52490