title: Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in aging rats: involvement with NO-sGC-cGKs pathway.
abstract: Declined vasorelaxation function in aging resistance arteries is responsible for aging-related multiple organ dysfunctions. The aim of the present study is to explore the role of peroxynitrite (ONOO-) in aging resistance arterial vasorelaxation dysfunction and the possible mechanism. In the present study, young (3-4 months olds) and aging (20 months olds) male SD rats were randomized to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger) for 2 weeks. The vasorelaxation of resistance arteries was determined in vitro; NOx level was tested by a colorimetric assay; the expression of nitrotyrosine (NT), soluble Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP), phosphorylated VASP (P-VASP) and cGMP in resistance arteries were detected by immunohistochemical staining. In the present study, endothelium-dependent dilation in aging resistance arteries was lower than in those from young rats (young vs. aging: 68.0% ± 4.5% vs. 50.4% ± 2.9%, P<0.01). And the endothelium-independent dilation remained constant. Compared with young rats, aging increased nitrative stress in resistance arteries, evidenced by elevated NOx production in serum (5.3 ± 1.0 nmol/ml vs. 3.3 ± 1.4 nmol/ml, P<0.05) and increased NT expression (P<0.05). ONOO- was responsible for the vasorelaxation dysfunction, evidenced by normalized vasorelaxation after inhibit ONOO- or its sources (P<0.05) and suppressed NT expression after FeTMPyP treatment (P<0.05). The expression of sGC was not significantly different between young and aging resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker of NO-sGC-cGKs signaling) decreased, which was reversed by FeTMPyP treatment in vivo (P<0.05). The present study suggested that ONOO- mediated the decline of endothelium-dependent vasorelaxation of aging resistance arteries by induction of the NO-sGC-cGKs pathway dysfunction.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Shang
authors.affiliation: Department of Chest Surgery, First Hospital of Longyan, Fujian Medical University, Fujian, PR China.
authors.forename: Chengzhang
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Pathology, Luhe Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhen
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China; Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease, Beijing, PR China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006339:Heart Rate; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000109:Acetylcholine