Sympathetic activation increases NO release from eNOS but neither eNOS nor nNOS play an essential role in exercise hyperemia in the human forearm

Abstract

Nitric oxide (NO) release from endothelial NO synthase (eNOS) and/or neuronal NO synthase (nNOS) could be modulated by sympathetic nerve activity and contribute to increased blood flow after exercise. We examined the effects of brachial-arterial infusion of the nNOS selective inhibitor S-methyl-l-thiocitrulline (SMTC) and the nonselective NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) on forearm arm blood flow at rest, during sympathetic activation by lower body negative pressure, and during lower body negative pressure immediately after handgrip exercise. Reduction in forearm blood flow by lower body negative pressure during infusion of SMTC was not significantly different from that during vehicle (-28.5 ± 4.02 vs. -34.1 ± 2.96%, respectively; P = 0.32; n = 8). However, l-NMMA augmented the reduction in forearm blood flow by lower body negative pressure (-44.2 ± 3.53 vs. -23.4 ± 5.71%; n = 8; P < 0.01). When lower body negative pressure was continued after handgrip exercise, there was no significant effect of either l-NMMA or SMTC on forearm blood flow immediately after low-intensity exercise (P = 0.91 and P = 0.44 for l-NMMA vs. saline and SMTC vs. saline, respectively; each n = 10) or high-intensity exercise (P = 0.46 and P = 0.68 for l-NMMA vs. saline and SMTC vs. saline, respectively; each n = 10). These results suggest that sympathetic activation increases NO release from eNOS, attenuating vasoconstriction. Dysfunction of eNOS could augment vasoconstrictor and blood pressure responses to sympathetic activation. However, neither eNOS nor nNOS plays an essential role in postexercise hyperaemia, even in the presence of increased sympathetic activation.

Keywords: endothelial nitric oxide synthase; exercise; forearm blood flow; neuronal nitric oxide synthase; sympathetic vasoconstriction.

Fig. 1.

Schematic of study protocols. Forearm blood flow (FBF) was measured by using venous occlusion plethysmography. A: effect of low body negative pressure (LBNP) on FBF was measured during infusion of N^G-monomethyl-l-arginine (l-NMMA; 2 μmol/min) and vehicle, and S-methyl-l-thiocitrulline (SMTC; 0.2 μmol/min) and vehicle. B: effect of LBNP on FBF was measured during infusion of propranolol and vehicle. C: effect of low- and high-intensity hand-grip exercise on FBF was measured in the presence of l-NMMA and vehicle and also with vehicle throughout. D: effect of simultaneous LBNP with low- and high-intensity exercise on FBF was measured in the presence of l-NMMA, SMTC, and saline control in a cross-over study.

Fig. 2.

A: FBF at rest and during LBNP during infusion of saline and l-NMMA. *P < 0.01 vs. saline with no LBNP; **P < 0.001 vs. saline with no LBNP; †P < 0.001 vs. l-NMMA with no LBNP. B: FBF at rest and during LBNP during infusion of saline and SMTC. *P < 0.001 vs. saline with no LBNP; **P < 0.01 vs. saline with no LBNP; †P < 0.01 vs. SMTC with no LBNP. C: percent change in FBF during l-NMMA and SMTC with LBNP. *P < 0.01 vs. SMTC (+, LBNP; −, no LBNP).

Fig. 3.

A: comparison of FBF after undertaking low- and high-intensity exercise, during saline or l-NMMA infusion. There was no significant difference in FBF during l-NMMA infusion when compared with saline during either low-intensity exercise (P = 0.22, n = 11) or high-intensity exercise (P = 0.32, n = 11). B: a comparison of the FBF immediately after low- and high-intensity exercise and LBNP while infusing saline, l-NMMA, or SMTC. There is no significant difference in FBF during l-NMMA or SMTC infusion when compared with saline, for either low-intensity exercise (P = 0.91 and P = 0.44, respectively; n = 10) or high-intensity exercise (P = 0.46 and P = 0.68, respectively; n = 10).