Neuronal nitric oxide synthase inhibition and regional sympathetic nerve discharge: Implications for peripheral vascular control

Neuronal nitric oxide (NO) synthase (nNOS) inhibition with systemically administered S-methyl-l-thiocitrulline (SMTC) elevates mean arterial pressure (MAP) and reduces rat hindlimb skeletal muscle and renal blood flow. We tested the hypothesis that those SMTC-induced cardiovascular effects resulted, in part, from increased sympathetic nerve discharge (SND). MAP, HR, and lumbar and renal SND (direct nerve recordings) were measured in 9 baroreceptor (sino-aortic)-denervated rats for 20 min each following both saline and SMTC (0.56 mg/kg i.v.). SMTC increased MAP (peak ΔMAP: 50 ± 8 mmHg, p < 0.01) compared to saline. Lumbar and renal SND were not different between saline and SMTC conditions at any time (p > 0.05). The ΔSND between saline and SMTC conditions for the lumbar and renal nerves were not different from zero (peak ΔSND, lumbar: 2.0 ± 6.8%; renal: 9.7 ± 9.0%, p > 0.05 versus zero for both). These data support that SMTC-induced reductions in skeletal muscle and renal blood flow reported previously reflect peripheral nNOS-derived NO vascular control as opposed to increased sympathetic vasoconstriction.

► Previous reports show that nNOS inhibition (SMTC) reduces skeletal muscle and renal blood flow.
► This may reflect central (↑sympathetic nerve discharge, SND) or peripheral nNOS-mediated effects.
► Presently, systemically administered SMTC elevated MAP without impacting lumbar or renal SND.
► This, in conjunction with previous reports, supports important peripheral nNOS-derived NO vascular control.