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Am J Physiol Heart Circ Physiol 283: H2110-H2118, 2002. First published July 11, 2002; doi:10.1152/ajpheart.00454.2002
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Vol. 283, Issue 5, H2110-H2118, November 2002

Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors

Luciana V. Rossoni1,2, Mercedes Salaices1, Marta Miguel1, Ana M. Briones1, Louis A. Barker3, Dalton V. Vassallo2, and María J. Alonso1

1 Department of Pharmacology and Therapeutics, Faculty of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain; 2 Department of Physiological Sciences, Federal University of Espirito Santo, 29040-090, Brazil; and 3 Department of Pharmacology, Louisiania State University Health Sciences Center, New Orleans, Louisiana 70119

The involvement of nitric oxide (NO), prostaglandins, and calcium-dependent potassium channel (KCa) activators on the negative modulation of phenylephrine-induced contractions was evaluated on the isolated aorta and caudal (CAU) artery obtained from rats treated with ouabain for 5 wk to induce hypertension. In ouabain-treated rats, the reactivity to phenylephrine was reduced in the endothelium-intact aorta but not the CAU segments. Endothelial modulation of phenylephrine contraction, as demonstrated by endothelium removal, NO synthase (NOS) inhibition with Nomega -nitro-L-arginine methyl ester and aminoguanidine, as well as KCa inhibition with tetraethylammonium, was more pronounced in segments from ouabain-treated animals, and here greater effects were seen in the aorta than in CAU. An increased expression of endothelial NOS and neuronal NOS was seen in the aorta after ouabain treatment. In CAU, only endothelial NOS was detected and ouabain treatment did not alter its expression. These results suggest that ouabain-induced hypertension is accompanied by increased NO release derived from endothelial NOS and neuronal NOS and increased release of an endothelial hyperpolarizing factor that presumably opens KCa, all of which contribute to the increased negative modulation of the phenylephrine contraction.

nitric oxide; endothelial-dependent hyperpolarizing factor; phenylephrine


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