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A large blood pressure-raising effect of nitric oxide synthase inhibition in humansIn 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. alpha-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.
Document ID
20040141995
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Sander, M.
(University of Texas Southwestern Medical Center Dallas, TX, United States)
Chavoshan, B.
Victor, R. G.
Blomqvist, C. G.
Date Acquired
August 22, 2013
Publication Date
April 1, 1999
Publication Information
Publication: Hypertension
Volume: 33
Issue: 4
ISSN: 0194-911X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: 5T-32-HL07360-19
CONTRACT_GRANT: 5T-32 HL07360-21
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cardiopulmonary

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