title: Collagen-induced arthritis increases inducible nitric oxide synthase not only in aorta but also in the cardiac and renal microcirculation of mice.
abstract: Rheumatoid arthritis (RA) may promote endothelial dysfunction. This phenomenon requires further investigation, especially in collagen-induced arthritis (CIA), as it is considered the experimental model most similar to RA. The objectives of this study were to identify CIA-induced changes in noradrenaline (NE) and acetylcholine (ACh) responses in mice aortas that may suggest endothelial dysfunction in these animals. Moreover, we characterize CIA-induced modifications in inducible nitric oxide synthase (iNOS) expression in the aortas and cardiac and renal tissues taken from these mice that may be related to possible endothelial dysfunction. Male DBA/1J mice were immunized with 100 μg of emulsified bovine collagen type II (CII) plus complete Freund's adjuvant. Twenty-one days later, these animals received a boost of an additional 100 μg plus incomplete Freund's adjuvant. Fifteen days after the onset of the disease, aortic rings from CIA and control mice were challenged with NE and ACh in an organ bath. In these animals, iNOS was detected through immunohistochemical analysis of aorta, heart and kidneys. Plasma nitrite concentration was determined using the Griess reaction. CIA did not change NE or ACh responses in mice aorta but apparently increased the iNOS expression not only in aorta, but also in cardiac and renal microcirculation. In parallel, CIA reduced nitrite plasma concentration. In mice, CIA appears to increase the presence of iNOS in aorta, as well as in heart and in kidney microcirculation. This iNOS increase occurs apparently in parallel to a reduction of the bioavailability of NO. This phenomenon does not appear to change NE or ACh responses in aorta.
authors.affiliation: Laboratory of Pharmacology, Marília Medical School, Marília, SP, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Palma Zochio Tozzato
authors.affiliation: Discipline of Biochemistry, Marília Medical School, Marília, SP, Brazil.
authors.forename: E F
authors.initials: EF
authors.lastname: Taipeiro
authors.affiliation: Discipline of Human Embryology, Marília Medical School, Marília, SP, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Spadella
authors.affiliation: Discipline of Pathology, Marília Medical School, Marília, SP, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Marabini Filho
authors.affiliation: Discipline of Rheumatology, Marília Medical School, Marília, SP, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: de Assis
authors.affiliation: Faceres School of Medicine, São José Do Rio Preto, SP, Brazil.
authors.forename: C P
authors.initials: CP
authors.lastname: Carlos
authors.affiliation: Laboratory of Immunohistochemistry, Padre Albino School of Medicine, Catanduva, SP, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Girol
authors.affiliation: Laboratory of Pharmacology, Marília Medical School, Marília, SP, Brazil.
authors.forename: A B
authors.initials: AB
authors.lastname: Chies
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000503:physiopathology; D001682:Biological Availability; D002417:Cattle; D024043:Collagen Type II; D003326:Coronary Circulation; D004727:Endothelium / Q000503:physiopathology; D005620:Freund's Adjuvant; D007668:Kidney / Q000098:blood supply / Q000201:enzymology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008833:Microcirculation; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D009573:Nitrites / Q000097:blood; D009638:Norepinephrine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D024043:Collagen Type II; D009573:Nitrites; D005620:Freund's Adjuvant; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000109:Acetylcholine; D009638:Norepinephrine
keywords: aorta; endothelium; experimental arthritis; oxidative stress; rheumatoid arthritis