title: Increased constrictor tone induced by ouabain treatment in rats.
abstract: Ouabain (Oua)-induced hypertension in rodents provides a model to study cardiovascular changes associated with human hypertension. We examined vascular function in rats after a long-term treatment with Oua. Systolic blood pressure was measured by tail-cuff plethysmography in male Sprague-Dawley rats treated with Oua (≈ 25 µg/d) or placebo for 8 weeks. Blood pressure increased in Oua-treated animals, reaching 30% above baseline systolic blood pressure after 7 weeks. At the end of treatment, vascular responses were studied in mesenteric resistance arteries (MRAs) by wire myography. Contraction to potassium chloride in intact and denuded arteries showed greater sensitivity in Oua-treated animals. Contraction to phenylephrine and relaxation to acetylcholine were similar between groups with a lower response to sodium nitroprusside in Oua-treated arteries. Sensitivity to endothelin-1 was higher in Oua-treated arteries. Na⁺-K⁺ ATPase activity was decreased in MRAs from Oua-treated animals, whereas protein expression of the Na⁺-K⁺ ATPase α₂ isoform was increased in heart and unchanged in mesenteric artery. Preincubation with indomethacin (10⁻⁵ M) or Nω-nitro-L-arginine methyl ester (10⁻⁴ M) abolished the differences in potassium chloride response and Na⁺-K⁺ ATPase activity. Changes in MRAs are consistent with enhanced vascular smooth muscle cell reactivity, a contributor to the increased vascular tone observed in this model of hypertension.
authors.affiliation: Biomedical Research Infrastructure Center, Winston-Salem State University, Winston Salem, NC 27101, USA. vpulgar@wakehealth.edu
authors.forename: Victor M
authors.initials: VM
authors.lastname: Pulgar
authors.forename: Anne B
authors.initials: AB
authors.lastname: Jeffers
authors.forename: Hanadi M
authors.initials: HM
authors.lastname: Rashad
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
authors.forename: Azeez A
authors.initials: AA
authors.lastname: Aileru
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009215:Myometrium / Q000201:enzymology / Q000378:metabolism; D010042:Ouabain / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010042:Ouabain; C498532:Atp1a2 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase