Vasopressin induces vascular superoxide via endothelin-1 in mineralocorticoid hypertension.
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 ETA 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 (beta-Mercapto-beta, beta-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.
Li
Lixin
L
Department of Pharmacology and Toxicology, B403 Life Sciences Building, Michigan State University, East Lansing, MI 48824-1317, USA.
Galligan
James J
JJ
Fink
Gregory D
GD
Chen
Alex F
AF
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism*; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000096:biosynthesis*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D014667:Vasopressins / Q000096:biosynthesis / Q000494:pharmacology*
D019332:Endothelin-1; D017483:Receptors, Vasopressin; D014667:Vasopressins; D013481:Superoxides; D003900:Desoxycorticosterone