title: Disturbance of vasodilation via protease-activated receptor 2 in SHRSP.Z-Lepr fa/IzmDmcr rats with metabolic syndrome.
abstract: Protease-activated receptor-2 (PAR2) activation causes vascular inflammation and vasodilation, but its role in metabolic syndrome (MetS) remains uncertain. Therefore, we examined whether the PAR2-induced vasodilation of SHRSP.Z-Lepr(fa)/IzmDmcr rats (SHRSP.ZF) is impaired and if so, whether administering telmisartan is protective. PAR2-activating peptide, 2-furoyl-LIGRLO-amide (2fly), relaxed the isolated superior and first-order branches of mesenteric arteries (MAs) from Wistar-Kyoto rats (WKY) and SHRSP.ZF. Superior-MA relaxation by 2fly was less in SHRSP.ZF than in WKY. Relaxation of first-order MAs by 2fly was the same in SHRSP.ZF and WKY. NO synthase inhibitor partially reduced 2fly-induced relaxation of superior and first-order MAs in SHRSP.ZF and WKY; inhibition of relaxation was proportionately larger in SHRSP.ZF. In SHRSP.ZF, nitroprusside-induced relaxation and the expression of soluble guanylyl cyclase decreased. In SHRSP.ZF, telmisartan reversed these abnormalities, and decreased blood pressure and serum levels of thiobarbituric acid reactive substances, an index of oxidative stress. Vasodilation via PAR2 activation was preserved in small-caliber MAs, in contrast to large-caliber MAs, even when MetS reduced NO-dependent relaxation mechanisms. NO and non-NO relaxing factor(s) contributed to PAR2-mediated relaxation in MAs, and the balance between factors may be altered to preserve vasodilation in MetS. Telmisartan prevented vascular dysfunction in MetS by protecting arteries against oxidative stress.
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan. Electronic address: skagota@mukogawa-u.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Kagota
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Wakuda
authors.affiliation: Cardiovascular Research Group, Division of BioMedical Sciences, Memorial University, St. John's, Newfoundland and Labrador, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: McGuire
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshikawa
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shinozuka
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D044464:Receptor, PAR-2 / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D000077333:Telmisartan; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C487404:2-furoyl-LIGRLO-amide; D001562:Benzimidazoles; D001565:Benzoates; D009842:Oligopeptides; D044464:Receptor, PAR-2; D018160:Receptors, Cytoplasmic and Nuclear; D017392:Thiobarbituric Acid Reactive Substances; D009599:Nitroprusside; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D000077333:Telmisartan
keywords: Endothelium dysfunction; Metabolic syndrome; Nitric oxide; Obesity; Protease-activated receptor 2