The effect of NG-nitro-L-arginine methyl ester upon basal blood flow and endothelium-dependent vasodilatation in the dog hindlimb.

Abstract

1. The role played by the endothelium-derived relaxing factor (EDRF), nitric oxide (NO) in the regulation of blood flow to the skeletal muscle vasculature of the dog skinned hindlimb has been determined by examining the effects of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) upon (i) basal iliac artery blood flow, (ii) vasodilator responses to endothelium-dependent and -independent agonists and (iii) reactive hyperaemic responses to arterial occlusion. 2. L-NAME (0.1-3 mg min-1) infused directly into the iliac artery dose-dependently reduced basal iliac artery blood flow by a maximum of 48.6 +/- 6.9% (n = 4) and also increased mean systemic arterial blood pressure by 25.6 +/- 5.0 mmHg (n = 4) (at 3 mg min-1 L-NAME). 3. Over the same dose range, L-NAME also inhibited the peak vasodilator responses to intra-arterially administered, submaximal bolus doses of the endothelium-dependent agonists, bradykinin (3-300 ng) and acetylcholine (30-300 ng) by approximately 40%. In contrast, peak vasodilator responses to the endothelium-independent agonists, sodium azide (3-30 micrograms) and adenosine (0.3-1 mg), and peak reactive hyperaemic responses to arterial occlusion (60 s) were largely unaffected by L-NAME. 4. The dose-related effects of L-NAME on basal iliac artery blood flow, mean systemic arterial blood pressure and endothelium-dependent vasodilator responses were significantly attenuated by pretreatment with L-arginine (100 mg min-1) followed by co-infusion of L-arginine (100 mg min-1) with L-NAME. 5. In conclusion, these data suggest that NO plays some role in regulating basal blood flow and in mediating the vasodilator responses to the endothelium-dependent agonists bradykinin and acetylcholine in the skeletal muscle vasculature of the dog hindlimb. The substantial component (~60%) of the peak vasodilator responses to bradykinin and acetylcholine, unaffected by L-NAME, may be independent of NO, or be mediated by an alternative EDRF-dependent but L-NAME-insensitive mechanism.