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-O2 peak) as determined on a maximal incremental test. Each horse underwent one control (C) and one (NO-synthase inhibitor; NG-L-nitroarginine 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-O2. However, at peak running speed in the L-NAME trial, an elevated O-2 extraction (P < 0.05) was not sufficient to prevent V-O2 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. (C) 2000 Elsevier Science B.V. All rights reserved.