title: Cyclooxygenase pathway is involved in the vascular reactivity and inhibition of the Na+, K+-ATPase activity in the tail artery from L-NAME-treated rats.
abstract: L-NAME (LN) induces hypertension by blocking nitric oxide (NO) synthesis. It produces vascular hyperreactivity to phenylephrine (PHE) associated with a reduced vascular Na+, K+-ATPase activity. The aim of this work was to investigate whether products of the cyclooxygenase pathway are involved in alterations of vascular reactivity and Na+-pump activity in the tail artery from LN-induced hypertension rats. Four groups of rats were used: Control (CT, normotensive), LN (50 mg/kg/day, hypertensive), indomethacin (Indo-4 mg/kg/day, normotensive), and LN plus Indo (LN + Indo, partially prevented hypertension). All drugs were administered in drinking water during 7 days. In isolated rat tail vascular beds; the reactivity to PHE, acetylcholine (ACh), sodium nitroprusside (SNP), the functional activity of the Na+, K+-ATPase (K+-induced relaxation) and the modulation of PHE-induced vasoconstriction by constitutively available NO were evaluated. LN increased vascular sensitivity (pD2) and reactivity (Emax) to PHE and Indo blocked the effect of LN on Emax without changing pD2. Emax and pD2 values for ACh were reduced by LN and partially reverted by Indo. SNP-induced vasodilatation was similar in all groups. LN reduced the activity of Na+, K+-ATPase and Indo prevented LN effects. LN also abolished NO ability to modulate PHE-induced contractions. This effect was partially prevented by Indo suggesting that products from the cyclooxygenase pathway might reduce NO actions. Indo itself did not affect vascular reactivity to PHE, ACh or SNP or the Na+,K+-ATPase activity. Results suggested that products from cyclooxygenase pathway are involved in the genesis or maintenance of LN-induced hypertension, playing a role in the increased vascular reactivity, in the reduction of the endothelium-dependent relaxation and in the inhibition of the functional activity of the Na+, K+-ATPase.
authors: Departamento de Ciências Fisiológicas, Centro Biomédico, Universidade Federal do Espírito Santo, Brazil.
authors: Leonardo
authors: L
authors: dos Santos
authors: Fabiano E
authors: FE
authors: Xavier
authors: Dalton V
authors: DV
authors: Vassallo
authors: Luciana V
authors: LV
authors: Rossoni
mesh_terms: D000465:Algorithms; D000818:Animals; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011451:Prostaglandin-Endoperoxide Synthases; D000254:Sodium-Potassium-Exchanging ATPase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin