IMPORTANCE OF NITRIC-OXIDE IN CANINE FEMORAL CIRCULATION - COMPARISON OF 2 NO INHIBITORS

Objective: The aim was to assess the importance of endothelium derived nitric oxide (NO) in the regulation of vascular tone in the limbs. Changes in the canine femoral circulation were investigated after inhibition of NO synthesis. Methods: The effects of two NO inhibitors, N(G)-monomethyl-L-arginine (LNMMA) and N(G)-nitro-L-arginine (NOARG), were compared on basal femoral blood flow and on endothelium dependent (acetylcholine) and endothelium independent (glyceryl trinitrate) vasodilatation in 15 pentobarbitone anaesthetised mongrel dogs. An electromagnetic flow probe was placed on the femoral artery to measure femoral blood flow. One catheter was advanced into the femoral artery proximal to the flow probe for blood pressure recording and another catheter distal to the flow probe for drug infusions. Results: LNMMA (0.28-mu-mol.ml-1) reduced basal femoral blood flow by 44(SEM 3)%, NOARG (0.07-mu-mol.ml-1) by 21(4)%, and NOARG (0.56-mu-mol.ml-1) by 29(3)%. The flow responses to acetylcholine were reduced after LNMMA by 27(8)%, unaltered after NOARG (0.07-mu-mol.ml-1), and reduced after NOARG (0.56-mu-mol.ml-1) by 60(7)%. The flow response to glyceryl trinitrate was unaltered. L-arginine re-established femoral blood flow after infusion of LNMMA and NOARG (0.07-mu-ml.ml-1), but L-arginine did not re-establish femoral blood flow after NOARG (0.56-mu-mol.ml-1), even when infused in a 60-fold molar excess. Conclusions: There is a continuous basal release of NO in the canine femoral circulation. The results obtained by infusing LNMMA suggest that more than 40% of basal femoral blood flow is mediated by endothelium derived NO. Whereas LNMMA was more potent than NOARG in reducing basal NO release, NOARG (0.56-mu-mol.ml-1) reduced acetylcholine induced vasodilation by as much as 60%.