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

Abstract

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.