Nitric oxide synthase inhibition with L-NAME reduces maximal oxygen uptake but not gas exchange threshold during incremental cycle exercise in man

Abstract

We hypothesized that the effective inhibition of nitric oxide synthase (NOS), achieved via systemic infusion of N(G)-nitro-l-arginine methyl ester (l-NAME), would reduce the gas exchange threshold (GET) and the maximal oxygen uptake (V(.)(O(2)max)) during incremental cycle exercise in man if NO is important in the regulation of muscle vasodilatation. Seven healthy males, aged 18-34 years, volunteered to participate in this ethically approved study. On two occasions, the subjects completed an incremental exercise test to exhaustion on an electrically braked cycle ergometer following the infusion of either l-NAME (4 mg kg(-1) in 50 ml saline) or placebo (50 ml saline, CON). At rest, the infusion of l-NAME resulted in a significant increase in mean arterial pressure (MAP; CON vs. l-NAME, 89 +/- 8 vs. 103 +/- 11 mmHg (mean +/- s.d.; P < 0.05)) and a significant reduction in heart rate (HR; CON vs. l-NAME, 60 +/- 12 vs. 51 +/- 8 beats min(-1); P < 0.01). At submaximal work rates, there was no significant difference in V(.)(O(2)) between the conditions and no difference in the GET (CON vs. l-NAME, 1.94 +/- 0.47 vs. 2.01 +/- 0.41 l min(-1)). However, at higher work rates, differences in V(.)(O(2)) between the conditions became more pronounced such that V(.)(O(2)max) was significantly lower with l-NAME (CON vs. l-NAME, 4.02 +/- 0.41 vs. 3.80 +/- 0.34 l min(-1); P < 0.05). The reduction in V(.)(O(2)max) was associated with a reduction in HR(max) (CON vs. l-NAME, 186 +/- 10 vs. 178 +/- 7 beats min(-1); P < 0.01). These results demonstrate that NOS inhibition with l-NAME has no effect on GET but reduces V(.)(O(2)max) during large muscle group exercise in man, presumably by direct or indirect effects on cardiac output and muscle blood flow.

Figure 1. Influence of the infusion of saline (control) and of a NOS-inhibitor (l-NAME) on mean arterial blood pressure over 60 min

Filled bars, control; open bars, l-NAME. *P < 0.05; **P < 0.01.

Figure 2. Influence of the infusion of saline (control) and of a NOS-inhibitor (l-NAME) on heart rate over 60 min

Filled bars, control; open bars, l-NAME. *P < 0.05; **P < 0.01.

Figure 3. Heart rate response to incremental exercise in the control and l-NAME conditions

Filled bars, control; open bars, l-NAME. Values are reported at the onset of the test (time 0), for every minute of the test up to minute 10, and at exhaustion (Max). *P < 0.05; **P < 0.01.

Figure 4. Pulmonary oxygen uptake response to incremental exercise in the control and l-NAME conditions

Filled bars, control; open bars, l-NAME. Values are reported at the onset of the test (time 0), for every minute of the test up to minute 10, and at exhaustion (Max). *P < 0.05; **P < 0.01.

Figure 5. Determination of the gas exchange threshold (GET) using a ‘cluster’ of gas exchange indices

Upper left panel illustrates the metabolic rate at which there is a disproportionate increase in CO₂ output (‘V-slope’ method; Beaver et al. 1986); lower left panel shows the ventilatory equivalents for O₂ and CO₂; upper right panel shows the respiratory exchange ratio; and lower right panel shows the end-tidal gas tension responses to exercise following the inhibition of nitric oxide synthase (○) and following a placebo infusion (•) in a typical subject. See text for further information. GET in each condition is shown by the open and filled arrows, respectively. There was no significant difference in the group mean GET between conditions.

Figure 6. Oxygen uptake response to incremental exercise following the inhibition of nitric oxide synthase (○) and following a placebo infusion (•) in a typical subject

Note the appreciable reduction in maximal oxygen uptake following nitric oxide synthase inhibition.