INHIBITION OF NO SYNTHASE PREVENTS ACUTE COLLATERAL ARTERY DILATION IN THE RAT HINDLIMB

The role of endothelium-derived nitric oxide (EDNO) in the initial ope ning and sustained dilation of collateral vessels in the peripheral ci rculation was investigated, Abrupt arterial occlusion was produced by clamping the rat superficial femoral artery (SFA). Arterial pressures were measured proximal (MAP) and distal (P-D) to the occlusion site. I n one group (INITIAL DILATION), the clamp was removed after P-D reache d a plateau, and then the nitric oxide synthase inhibitor, N omega-nit ro-L-arginine methyl ester (L-NAME), was administered and the occlusio n repeated in the same limb to evaluate the role of nitric oxide in th e initial opening of collateral vessels, In another group (SUSTAINED D ILATION), L-NAME was administered after acute compensation to SFA occl usion had occurred to determine if inhibition of nitric oxide synthase would reverse any acute compensation, Collateral dilation was evaluat ed by recovery in P-D relative to MAP (P-D-%MAP) and by the percent of total resistance in the collateral-dependent circuit due primarily to collaterals (%R(c)) The acute compensation indicated by an increase i n P-D-%MAP (14 +/- 1.9% to 27 +/- 2.6%) and decrease in %R(c) (86 +/- 1.9 to 73 +/- 2.6%) in the INITIAL DILATION group was prevented by L-N AME (P < 0.0005). L-NAME also reversed the compensation in the SUSTAIN ED DILATION group; P-D-%MAP decreased from 28 +/- 2.3% to 11 +/- 1.9% and %R(c) increased from 72 +/- 2.3% to 93 +/- 1.1% after administrati on of L-NAME, Although collateral how was not measured, the results ar e consistent with the hypothesis that acute collateral dilation is med iated by increases in how or shear stress which stimulate the release of EDNO. (C) 1996 Academic Press, Inc.