title: Importance of the angiotensin type 1 receptor in angiotensin II-induced bronchoconstriction and bronchial hyperresponsiveness in the guinea pig.
abstract: Although angiotensin II (Ang II) causes bronchoconstriction and bronchial hyperresponsiveness to methacholine in mildly asthmatic patients, the responsible mechanisms for these reactions are unclear. The authors examined the effect of intravenous infusion of Ang II on airway constriction in guinea pigs. Furthermore, the effects of subthreshold concentrations of Ang II on bronchial responsiveness to methacholine were investigated. Airway opening pressure (Pao), an index of bronchoconstriction, increased dose dependently after intravenous infusion of 3 and 10 nmol/kg Ang II (72.2 and 236.5 increase above the baseline value, respectively). In another set of experiments, animals received a methacholine inhalation challenge under a constant intravenous infusion of a subthreshold dose of Ang II (2 nmol/kg/min). The Ang II infusion elicited bronchial hyperresponsiveness to methacholine. The provocative concentration of methacholine, which produced a 200% increase above the baseline Pao (PC200), decreased from 306.9 to 156.1 micrograms/mL upon Ang II infusion. Pretreatment with TCV-116, a type 1 Ang II (AT1) receptor antagonist, but not PD123319, a type 2 Ang II (AT2) receptor antagonist, dose dependently prevented both the Ang II-induced bronchoconstriction and bronchial hyperresponsiveness to methacholine. The authors conclude that Ang II caused bronchoconstriction and induced bronchial hyperresponsiveness to methacholine via the AT1 receptors and that this effect did not involve the release of other bronchoactive mediators.
authors.affiliation: Division of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan. watanabe@med3.m.kanazawa-u.ac.jp
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Myou
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Hideki
authors.initials: H
authors.lastname: Tachibana
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Sinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013618:Tachyphylaxis; D013777:Tetrazoles; D014230:Triazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018927:Anti-Asthmatic Agents; D000959:Antihypertensive Agents; D001381:Azepines; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001643:Bridged Bicyclo Compounds; D016085:Bronchoconstrictor Agents; D002867:Chromones; D005229:Fatty Acids, Monounsaturated; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014230:Triazoles; D014662:Vasoconstrictor Agents; D016210:Methacholine Chloride; D000804:Angiotensin II; C056566:S 145; C073402:PD 123319; C068033:E 6123; C077793:candesartan cilexetil; D002211:Capsaicin; C047681:pranlukast