Hypertension, Vol 21, 359-363, Copyright © 1993 by American Heart Association
J Dananberg, RS Sider and RJ Grekin
To study the hemodynamic and metabolic effects of chronic inhibition of
endothelium-derived nitric oxide, we treated conscious rats with an oral
solution of N omega-nitro-L-arginine (LNA), an inhibitor of nitric oxide
production by endothelial cells. After 3 days of treatment with 2.74 mM
LNA, rats had higher blood pressures (136 +/- 5 versus 113 +/- 3 mm Hg, p
< 0.0005) than did the control animals. This effect was maintained
through 7 days of treatment (142 +/- 6 versus 109 +/- 4 mm Hg, p <
0.0005) and in three animals for 35 days (167 +/- 7 mm Hg). The blood
pressure rise was dose dependent. The hypertensive effect of oral LNA was
not enhanced by the administration of 20 mg intraperitoneal LNA and was
prevented by pretreatment with L-arginine, although L-arginine also caused
a transient but significant increase in urinary sodium excretion. When LNA
treatment was discontinued, blood pressure fell gradually, with an
effective biological half-life of 4.2 days. Metabolic balance studies did
not identify differences in sodium or potassium balance between treated and
control animals. Plasma renin activity was lower in LNA-treated animals,
and aldosterone concentrations tended to be lower. In contrast, atrial
natriuretic factor levels and serum electrolyte concentrations were
unchanged after 7 days of treatment with LNA. These data support the
premise that endothelium-derived nitric oxide plays an important role in
basal hemodynamic homeostasis. Oral administration of LNA may serve as a
model of chronic nitric oxide-deficient hypertension and allow for the
future study of endothelium dependence in hypertension.
ARTICLES
Sustained hypertension induced by orally administered nitro-L-arginine
Division of Endocrinology, University of Michigan, Ann Arbor 48109-0678.
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