title: Alterations in phenylephrine-induced contractions and the vascular expression of Na+,K+-ATPase in ouabain-induced hypertension.
abstract: Hypertension development, phenylephrine-induced contraction and Na(+),K(+)-ATPase functional activity and protein expression in aorta (AO), tail (TA) and superior mesenteric (SMA) arteries from ouabain- (25 microg day(-1), s.c., 5 weeks) and vehicle-treated rats were evaluated. Ouabain treatment increased systolic blood pressure (127+/-1 vs 160+/-2 mmHg, n=24, 35; P<0.001) while the maximum response to phenylephrine was reduced (P<0.01) in AO (102.8+/-3.9 vs 67.1+/-10.1% of KCl response, n=12, 9) and SMA (82.5+/-7.5 vs 52.2+/-5.8%, n=12, 9). Endothelium removal potentiated the phenylephrine response to a greater extent in segments from ouabain-treated rats. Thus, differences of area under the concentration-response curves (dAUC) in endothelium-denuded and intact segments for control and ouabain-treated rats were, respectively: AO, 56.6+/-9.6 vs 198.3+/-18.3 (n=9, 7); SMA, 85.5+/-15.4 vs 165.4+/-24.8 (n=6, 6); TA, 13.0+/-6.1 vs 39.5+/-10.4% of the corresponding control AUC (n=6, 6); P<0.05. The relaxation to KCl (1 - 10 mM) was similar in segments from both groups. Compared to controls, the inhibition of 0.1 mM ouabain on KCl relaxation was greater in AO (dAUC: 64.8+/-4.6 vs 84.0+/-5.1%, n=11, 14; P<0.05), similar in SMA (dAUC: 39.1+/-3.9 vs 43.3+/-7.8%, n=6, 7; P>0.05) and smaller in TA (dAUC: 62.1+/-5.5 vs 41.4+/-8.2%, n=12, 13; P<0.05) in ouabain-treated rats. Protein expression of both alpha(1) and alpha(2) isoforms of Na(+),K(+)-ATPase was augmented in AO, unmodified in SMA and reduced in TA from ouabain-treated rats. These results suggest that chronic administration of ouabain induces hypertension and regional vascular alterations, the latter possibly as a consequence of the hypertension.
authors.affiliation: Department of Pharmacology and Therapeutics, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: Jesús
authors.initials: J
authors.lastname: Marín
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
authors.forename: María J
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006973:Hypertension / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000201:enzymology; D010042:Ouabain / Q000008:administration & dosage*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013623:Tail / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase