La. Fortepiani et al., Effect of endothelin blockade on pressure natriuresis in nitric oxide-deficient hypertensive rats, J HYPERTENS, 17(2), 1999, pp. 287-291
Citations number
23
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective Chronic inhibition of nitric oxide synthesis has been shown to ca
use arterial hypertension and an important blunting of the pressure diuresi
s and natriuresis response. The mechanisms mediating these abnormalities ar
e not completely established. We therefore studied the effects of endotheli
n on these alterations.
Materials and methods Pressure diuretic and natriuretic relationships were
evaluated in rats treated chronically (3 weeks) with the nitric oxide synth
esis inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg per
day), alone or in combination with bosentan sodium salt (acute treatment: 1
0 mg/kg, intravenously; chronic treatment: 10 mg/kg per day).
Results Chronic treatment with L-NAME significantly elevated mean arterial
pressure (143.7 +/- 2.8 mmHg versus 102.8 +/- 1.6 in controls), reduced the
glomerular filtration rate and renal blood flow and shifted the pressure d
iuretic and natriuretic responses to the right. Treatment with bosentan, ei
ther acute or chronically, did not attenuate the arterial hypertension of t
he L-NAME-treated rats but normalized the glomerular filtration rate and re
nal blood flow. In spite of the normalization of renal hemodynamics, the pr
essure diuretic and natriuretic responses of the bosentan-treated groups we
re not normalized, although chronic bosentan significantly improved the pre
ssure natriuretic response.
Conclusions These results indicate that endothelin participates in the rena
l hemodynamic and excretory alterations that follow chronic inhibition of n
itric oxide synthesis. However, the arterial hypertension is not mediated b
y endothelin activation. (C) Lippincott Williams & Wilkins.