Efficiency of
NO Donors in Substituting Impaired Endogenous NO
Production: a Functional and Morphological Study
M.
GEROVÁ, F. KRISTEK
Institute
of Normal and Pathological Physiology, Slovak
Academy of Sciences, Bratislava, Slovak Republic
Received
May 9, 2000
Accepted August 4, 2000
Summary
Two exogenous NO donors were used to act as
substitutes for impaired endogenous nitric oxide
(NO) production due to inhibition of NO synthase
in rats. Six weeks' lasting inhibition of NO
synthase by NG-nitro-L-arginine methyl ester
(L-NAME) induced stabilized hypertension.
Simultaneously administered
isosorbide-5-mononitrate did not prevent the
development of hypertension. Molsidomine,
administered concomitantly with L-NAME,
significantly attenuated the BP increase.
However, BP was still found to be moderately
increased compared to the initial values.
Remarkable alterations in the geometry of the
aorta, carotid and coronary artery found in
NO-deficient hypertension were prevented in rats
administered L-NAME plus molsidomine at the same
time. In spite of 6 weeks' lasting inhibition of
NOS, the NOS activators acetylcholine and
bradykinin induced BP decrease; the maximum
hypotensive value did not differ from the values
recorded in the controls or in animals treated
with L-NAME plus molsidomine. Notably enough, the
hypotension was similar to that found in rats
administered L-NAME alone for six weeks. After NO
synthase inhibition, Isosorbide-5-mononitrate
does not substitute and molsidomine substitute
only partially the impaired endogenous NO
production.
Key
words
Nitric oxide · Hypertension · Conduit
arteries · Morphology · Molsidomine ·
Isosorbide-5-mononitrate · NOS activation
Reprint requests
Dr. M. Gerová, Institute of Normal and
Pathological Physiology, Slovak Academy of
Sciences, Sienkiewiczova 1, 813 71 Bratislava,
Slovak Republic. Fax +421-7-52968516, E-mail: gerova@unpf.savba.sk
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