title: Cyclooxygenase inhibition reduces blood pressure elevation and vascular reactivity dysfunction caused by inhibition of nitric oxide synthase in rats.
abstract: In the present study we investigated the role of cyclooxygenase (COX)-dependent vasoconstrictors in the hypertension and altered vascular reactivity following prolonged nitric oxide (NO) synthase inhibition. Male Wistar rats (250-270 g) were divided into four groups and treated for 7 days with Placebo (control), L-NAME (48 mg/kg/day), indomethacin (4 mg/kg/day) and L-NAME in combination with indomethacin. L-NAME treatment induced arterial hypertension, in vitro aortic hyperresponsiveness to phenylephrine, impaired vasodilatory response to acetylcholine and no significant change in response to sodium nitroprusside. Indomethacin co-treatment partially prevented blood pressure elevation, restored responsiveness to phenylephrine and improved sensitivity to acetylcholine. Indomethacin treatment alone did not modify blood pressure and aortic vascular reactivity. Both enhanced phenylphrine-induced contraction and impaired acetylcholine-evoked vasodilation induced by acute NO synthase inhibition with L-NAME (10(-4) M) in normal rat aortas were not modified by indomethacin (10(-5) M). These results are consistent with the hypothesis that constricting factors, which arise from the COX pathway, contribute to hypertension and altered vascular reactivity following continued inhibition of NO synthase.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil. Valdeci_da_Cunha@berlex.com
authors.forename: V
authors.initials: V
authors.lastname: da Cunha
authors.forename: L V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: P A
authors.initials: PA
authors.lastname: Oliveira
authors.forename: S
authors.initials: S
authors.lastname: Poton
authors.forename: S C
authors.initials: SC
authors.lastname: Pretti
authors.forename: D V
authors.initials: DV
authors.lastname: Vassallo
authors.forename: I
authors.initials: I
authors.lastname: Stefanon
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin