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(Hypertension. 1995;26:691-695.)
© 1995 American Heart Association, Inc.
Articles |
Sympathetically Mediated Hypertension Caused by Chronic Inhibition of Nitric Oxide
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 NB11.116, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-8573.
Abstract Pharmacological inhibition of nitric oxide synthase
causes sustained hypertension in many animal species. Although this
hypertension has been attributed to inhibition of
endothelium-dependent vasodilation, short-term
studies in anesthetized preparations have advanced the
hypothesis that there could be a sympathetic component to this
hypertension. To test this hypothesis we measured
intra-arterial pressure directly before and after 1
week of treatment with the nitric oxide synthesis inhibitor
N
-nitro-L-arginine methyl ester
(L-NAME, approximately 80 mg/kg per day in drinking water) in conscious
unrestrained rats with or without chronic guanethidine-induced
sympathectomy. The major new finding is that the
hypertensive response to L-NAME was greatly attenuated by
sympathectomy. With L-NAME, mean arterial
pressure increased from 101±3 to 152±6 mm Hg in rats without
sympathectomy (n=11) but only from 96±2 to 122±3
mm Hg in rats with sympathectomy (n=15, +52±5 versus
+27±4 mm Hg, P<.01). Sympathectomy did
not alter maximal endothelium-dependent
vasodilation assessed by femoral vascular responses to
intra-arterial acetylcholine or bradykinin, indicating
that the differing hypertensive responses to L-NAME in rats with versus
without sympathectomy could be related to inhibition of
neuronal rather than endothelial nitric oxide
synthesis. We also found that L-NAME–induced hypertension, once
developed, is completely reversed by acute ganglionic blockade. In
conclusion, these findings identify an important sympathetic neural
component to the sustained hypertension produced by pharmacological
inhibition of nitric oxide in the rat.
Key Words: nitric oxide • sympathetic nervous system • sympathectomy • rats • hypertension
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