(Hypertension. 1997;30:64-70.)
© 1997 American Heart Association, Inc.
Articles |
The Sympathetic Nervous System Is Involved in the Maintenance but Not Initiation of the Hypertension Induced by N
-Nitro-L-Arginine Methyl Ester
From the Division of Cardiology, Molecular Cardiology Laboratories, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Correspondence to Ronald G. Victor, MD, Molecular Cardiology Laboratories, Room NB11.200D, UT Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75235-8573. E-mail victor{at}ryburn.swmed.edu
Abstract Studies in anesthetized animals have
advanced the theory that there is an important neurogenic component to
the hypertension caused by pharmacological inhibition of nitric oxide,
but studies in conscious animals have produced conflicting evidence for
and against this theory. To try to reconcile the seemingly
contradictory data, we hypothesized that the neurogenic component of
this hypertension is time dependent such that the sympathetic nervous
system is involved primarily in the maintenance, rather than
the initiation, of the hypertension. We measured
intra-arterial pressure in conscious, unrestrained rats
with and without guanethidine-induced sympathectomy
during varying durations of intravenous
N-nitro-L-arginine methyl ester
(L-NAME). The major new finding is that sympathectomy
had no effect on the hypertensive response to bolus injections of
L-NAME but in the same rats it produced a greater than 50% attenuation
in the hypertension seen after 6 days of continuous L-NAME (change in
mean arterial pressure, 23±4 versus 55±4 mm Hg,
P<.01, sympathectomy versus control). Using
8-hour infusions of L-NAME, we found that 60 minutes was the minimum
time required for detecting a sympathectomy-sensitive
component of L-NAME–induced hypertension. Furthermore, we demonstrate
that the magnitude of this component increases further between 8 hours
to 6 days of continuous L-NAME: it accounted for only 18% of the total
hypertensive response at 8 hours but 61% after 6 days. From these
experiments, we conclude that the importance of the sympathetic system
in the pathogenesis of L-NAME–induced hypertension accrues slowly over
hours and days, and thus its importance can be overlooked by focusing
on the initial phase of the hypertension.
Key Words: nitric oxide • sympathetic nervous system • sympathectomy • L-NAME • endothelin
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