title: Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors.
abstract: The involvement of nitric oxide (NO), prostaglandins, and calcium-dependent potassium channel (K(Ca)) 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 N(omega)-nitro-L-arginine methyl ester and aminoguanidine, as well as K(Ca) 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 K(Ca), all of which contribute to the increased negative modulation of the phenylephrine contraction.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Autonomous University of Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: Marta
authors.initials: M
authors.lastname: Miguel
authors.forename: Ana M
authors.initials: AM
authors.lastname: Briones
authors.forename: Louis A
authors.initials: LA
authors.lastname: Barker
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
authors.forename: María J
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D010042:Ouabain / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D001685:Biological Factors; D002316:Cardiotonic Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006146:Guanidines; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D010656:Phenylephrine; D009569:Nitric Oxide; D010042:Ouabain; D019789:Tetraethylammonium; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin