PMID: 8587446Jan 1, 1995Paper

Do ETA receptors participate in the hemodynamic and renal effects of chronic nitric oxide blockade?

Journal of Cardiovascular Pharmacology
C K FujiharaR Zatz

Abstract

Chronic nitric oxide (NO) blockade promotes progressive hypertension, marked renal vasoconstriction, and glomerular and renal interstitial injury. Inhibition of the renin/angiotensin system prevents only partially the functional and structural abnormalities associated with this model. Because endothelin (ET) is a powerful endogenous vasoconstrictor and promitogen, we examined the hypothesis that it might also mediate the hemodynamic and renal structural effects of chronic NO blockade. Four groups of 16 adult male Munich-Wistar rats were studied. Group C received daily i.p. saline injections and no drug treatment. Group C+FR received daily i.p. injections of the ETA inhibitor FR139317, 32 mg/kg. Group NAME received the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), 65 mg/kg/day in the drinking water, and group NAME+FR received both L-NAME and FR139317. At 2 weeks of treatment, renal and systemic hemodynamic parameters assessed under anesthesia were similar in Groups C and C+FR. Rats of Group NAME exhibited systemic hypertension and renal vasoconstriction characteristic of this model. FR139317 was ineffective in preventing these abnormalities in Group NAME+FR. In eight additional rats of each group observed at 30 da...Continue Reading

Citations

Nov 7, 2002·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jongun LeeSoo Wan Kim
Dec 18, 1998·Hypertension·R Zatz, C Baylis

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