Cardiorespiratory impact of the nitric oxide synthase inhibitor L-NAME in the exercising horse.

To investigate the role of nitric oxide, NO, in facilitating cardiorespiratory function during exercise, five horses ran on a treadmill at speeds that yielded 50, 80 and 100% of peak pulmonary oxygen uptake (V(O(2)) peak) as determined on a maximal incremental test. Each horse underwent one control (C) and one (NO-synthase inhibitor; N(G)-L-nitro-arginine methyl ester (L-NAME), 20 mg/kg) trial in randomized order. Pulmonary gas exchange (open flow system), arterial and mixed-venous blood gases, cardiac output (Fick Principle), and pulmonary and systemic conductances were determined. L-NAME reduced exercise tolerance, as well as cardiac output (C, 291+/-34; L-NAME, 246+/-38 L/min), body O(2) delivery (C, 74.4+/-5. 5; L-NAME, 62.1+/-5.6 L/min), and both pulmonary (C, 3.07+/-0.26; L-NAME, 2.84+/-0.35 L/min per mmHg) and systemic (C, 1.55+/-0.24; L-NAME, 1.17+/-0.16 L/min per mmHg) effective vascular conductances at peak running speeds (all P<0.05). On the 50 and 80% trials, L-NAME increased O(2) extraction, which compensated for the reduced body O(2) delivery and prevented a fall in V(O(2)). However, at peak running speed in the L-NAME trial, an elevated O(2) extraction (P<0. 05) was not sufficient to prevent V(O(2)) from falling consequent to the reduced O(2) delivery. At the 50 and 80% running speeds (as for peak), L-NAME reduced pulmonary and systemic effective conductances. These data demonstrate that the NO synthase inhibitor, L-NAME, induces a profound hemodynamic impairment at submaximal and peak running speeds in the horse thereby unveiling a potentially crucial role for NO in mediating endothelial function during exercise.