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Contribution of the endothelin and renin–angiotensin systems to the vascular changes in rats chronically treated with ouabain
Author(s) -
Xavier Fabiano E,
Yogi Álvaro,
Callera Gláucia E,
Tostes Rita C,
Alvarez Yolanda,
Salaices Mercedes,
Alonso María J,
Rossoni Luciana V
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705994
Subject(s) - ouabain , losartan , medicine , endocrinology , phenylephrine , angiotensin ii , endothelin receptor , enos , renin–angiotensin system , chemistry , endothelin 1 , receptor , nitric oxide , nitric oxide synthase , blood pressure , sodium , organic chemistry
Renin–angiotensin and endothelin systems are involved in the cardiovascular effects produced by treatment with ouabain. We recently demonstrated that the contractile response to phenylephrine is decreased in ouabain‐treated rats. The present study investigated whether endothelin‐1 (ET‐1) and angiotensin II (Ang II) contributes to the vascular changes observed in rats chronically treated with ouabain. Wistar rats were treated with ouabain (8.0 μ g day −1 , s.c. pellets for 5 weeks) alone or in combination with an endothelin type A receptor (ET A ) antagonist, BMS182874 (40 mg kg −1 day −1 , per gavage) or an angiotensin type 1 (AT 1 ) receptor antagonist, losartan (15 mg kg −1 day −1 , p.o.). Treatment with ouabain increased systolic blood pressure and treatment with either losartan or BMS182874 prevented the development of ouabain‐induced hypertension. The sensitivity and maximal response for phenylephrine were reduced in aortic rings from ouabain‐treated rats. Removal of the endothelium or in vitro exposure to an inhibitor of nitric oxide synthase (NOS), N ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 100 μ M ) increased the responses to phenylephrine, an effect that was more pronounced in aortas from ouabain‐treated rats. Endothelial NOS protein (eNOS) expression was increased after ouabain treatment. Treatment with BMS182874, but not with losartan, prevented the effects of ouabain on the reactivity of phenylephrine and in eNOS protein expression. Gene expression of pre–pro‐ET‐1 and ET A receptors was increased in aortic rings from ouabain‐treated rats. ET B receptor gene expression was not altered by ouabain treatment. In conclusion, our results suggest that endothelin and angiotensin systems play an important role in the development of ouabain‐induced hypertension. However, ET‐1, by activation of ET A receptors, but not Ang II, contributes to changes in vascular reactivity to phenylephrine induced by chronic treatment with ouabain.British Journal of Pharmacology (2004) 143 , 794–802. doi: 10.1038/sj.bjp.0705994