A Large Blood Pressure–Raising Effect of Nitric Oxide Synthase Inhibition in Humans

Publisher Website
Google Scholar
Abstract
—In experimental animals, systemic administration of nitric oxide synthase (NOS) inhibitors causes large increases in blood pressure that are in part sympathetically mediated. The aim of this study was to determine the extent to which these conclusions can be extrapolated to humans. In healthy normotensive humans, we measured blood pressure in response to two NOS inhibitors, NG-monomethyl-l-arginine (l-NMMA) and NG-nitro-l-arginine methyl ester (l-NAME), the latter of which recently became available for use in humans. The major new findings are 3-fold. First, l-NAME produced robust increases in blood pressure that were more than 2 times larger than those previously reported in humans with l-NMMA and approximated those seen in experimental animals. l-NAME (4 mg/kg) raised mean arterial pressure by 24±2 mm Hg (n=27, P<0.001), whereas in subjects who received both inhibitors, a 12-fold higher dose of l-NMMA (50 mg/kg) raised mean arterial pressure by 15±2 mm Hg (n=4, P<0.05 vs l-NAME). Second, the l-...