Published Online
on December 16, 2002

A more recent version of this article appeared on March 1, 2003

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Submitted on October 4, 2002
Revised on October 25, 2002

Vasopressin Induces Vascular Superoxide Via Endothelin-1 in Mineralocorticoid Hypertension

Lixin Li; James J. Galligan; Gregory D. Fink; and Alex F. Chen^*

From the Department of Pharmacology and Toxicology, and the Neuroscience Program, Michigan State University, East Lansing.

^* To whom correspondence should be addressed. E-mail: chenal{at}msu.edu.

Abstract—We have recently reported that endothelin-1 (ET-1), which is increased in the arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, stimulates superoxide production. However, the humoral mechanisms responsible for ET-1-induced superoxide formation in low-renin models of hypertension, such as DOCA-salt hypertension, remain undefined. Vasopressin is known to upregulate vascular preproET-1 gene expression in DOCA-salt rats, an effect that is absent in vasopressin-deficient Brattleboro rats treated with DOCA-salt. The present study tested the hypothesis that vasopressin contributes to ET-1-induced vascular superoxide production in DOCA-salt hypertensive rats. Carotid arterial segments of DOCA, sham (uninephrectomized), or normal (untreated) rats were used for the study. In vitro vasopressin treatment of carotid arteries from normal rats for 24 hours, but not 4 hours, increased both ET-1 and superoxide levels. The increase of vasopressin-induced superoxide was reduced by pretreatment of the vessels with ABT627, a selective ET_A receptor antagonist ABT627. Vasopressin, ET-1, and superoxide levels were significant elevated in carotid arteries of DOCA-salt rats compared with sham controls. The selective V1-vasopressin receptor antagonist (-Mercapto-, -cyclopentamethylenepropiony¹, O-Me-Tyr², Arg⁸ vasopressin, ME-AVP), decreased superoxide both in vasopressin-treated vessels of normal rats and in vessels of DOCA-salt rats, with a concomitant reduction of ET-1 content. These results suggest that vasopressin increases vascular superoxide levels by stimulating ET-1 formation in mineralocorticoid hypertension, and that V1-vasopressin receptors play an important role in this process.

Key words: vasopressin • endothelin • superoxide • hypertension, low renin

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