title: Deletion of inducible nitric oxide synthase decreases mesenteric vascular responsiveness in portal hypertensive mice.
abstract: The effects of pre-hepatic portal hypertension were examined on the responsiveness of aorta and mesenteric artery from wild-type, inducible nitric oxide synthase knockout (iNOS-KO) and endothelial nitric oxide synthase knockout (eNOS-KO) mice. Mice were sham-operated or made portal hypertensive by creating a calibrated portal vein stenosis. Acetylcholine produced marked relaxations in phenylephrine (10 microM) contracted aorta and mesenteric artery from wild-type and iNOS-KO, both sham and portal hypertensive, but relaxations were abolished in vessels from eNOS-KO mice. There were no significant differences between sham and portal hypertensive animals within groups in the effects of acetylcholine. The potency of KCl was significantly increased in aorta and mesenteric artery from eNOS-KO mice. The maximum contraction to the alpha(1)-adrenoceptor agonist phenylephrine was significantly increased in aorta from eNOS-KO, as compared with wild-type mice. There were no significant differences between sham and portal hypertensive animals within each group in contractions of aorta to KCl or phenylephrine. However, in mesenteric artery, although portal hypertension did not change responsiveness in wild-type or eNOS-KO as compared to sham animals, the potency of phenylephrine was significantly reduced in portal hypertensive iNOS-KO mice as compared to shams. Hence, portal hypertension as compared to sham operation did not affect responses to vasoconstrictors in mouse aorta, but in mouse mesenteric artery portal hypertension affected vascular responses in iNOS-KO mice, suggesting that iNOS is involved in the mesenteric vascular response to portal vein ligation.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Sotiria
authors.initials: S
authors.lastname: Bexis
authors.forename: Catherine
authors.initials: C
authors.lastname: Vandeputte
authors.forename: P Aiden
authors.initials: PA
authors.lastname: McCormick
authors.forename: James R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D003037:Cobalt Radioisotopes; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D003037:Cobalt Radioisotopes; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester