(Hypertension. 1999;33:937-942.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
A Large Blood Pressure–Raising Effect of Nitric Oxide Synthase Inhibition in Humans
From the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to Ronald G. Victor, MD, Hypertension Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-8586. E-mail rvicto{at}mednet.swmed.edu
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-NAME–induced increases
in blood pressure were caused specifically by NOS inhibition because
they were reversed by L-arginine (200 mg/kg, n=12) but not
D-arginine (200 mg/kg, n=6) and because
NG-nitro-D-arginine methyl ester
(4 mg/kg, n=5) had no effect on blood pressure. Third, in humans, there
is an important sympathetic component to the blood pressure–raising
effect of NOS inhibition. 
-Adrenergic blockade with
phentolamine (0.2 mg/kg, n=9) attenuated the
L-NAME–induced increase in blood pressure by 40%
(P<0.05). From these data, we conclude that
pharmacological inhibition of NOS causes large increases in blood
pressure that are in part sympathetically mediated in humans as well as
experimental animals.
Key Words: nitric oxide • blood pressure • L-NMMA • L-NAME • D-NAME • arginine • adrenergic receptor blockers
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