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Pharmacological inhibition of nitric oxide synthase increases sympathetic nerve activity in healthy humans
Author(s) -
Young Colin N.,
Fisher James P.,
Gallagher Kevin M.,
Fadel Paul J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.740.13
Subject(s) - baroreflex , nitric oxide synthase , baroreceptor , nitric oxide , medicine , vasodilation , endocrinology , blood pressure , inhibitory postsynaptic potential , anesthesia , mean arterial pressure , pharmacology , chemistry , heart rate
Animal studies have indicated that nitric oxide (NO) is a key signaling molecule involved in the tonic restraint of central sympathetic outflow from the brainstem. Extension of these findings to humans has been difficult since experimental systemic NO synthase (NOS) inhibition rapidly increases blood pressure (BP) from the removal of endothelial‐dependent vasodilation and activates an arterial baroreflex‐mediated sympathoinhibitory response. Thus, to overcome this confounding inhibitory influence of the baroreflex we measured skin SNA, which is not under baroreceptor control. Seven healthy subjects (26 ± 3 yr) were studied before, during and 90 minutes after a 60 minute intravenous infusion of the NOS inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME; 4mg/kg). Skin SNA and BP were continuously measured. Mean BP was increased from baseline at the end of the L‐NAME infusion (Δ15 ± 2 mmHg; P<0.05) and remained elevated at 90 minutes post infusion (Δ16 ± 1 mmHg; P<0.05). Similarly, skin SNA was elevated at the end of the L‐NAME infusion (ΔTotal Area 133 ± 59 au; P<0.05) and this increase was maintained at 90 minutes post infusion (ΔTotal Area 209 ± 70 au; P<0.05). Importantly, skin SNA remained unchanged during time control experiments. These preliminary findings suggest that pharmacological inhibition of NOS increases SNA and supports a role of NO in central sympathetic control in humans. Supported by NIH DK076636.