title: Modulation of bronchial reactivity by angiotensin-converting enzyme in unanesthetized guinea pigs.
abstract: To investigate the role of angiotensin-converting enzyme (ACE) in the modulation of bronchial reactivity, we tested the effects of a specific ACE inhibitor, captopril (CAP), on the bronchial reactivity to substance P (SP) and methacholine (MCH) in unanesthetized guinea pigs. The relative role of ACE on the vascular endothelium and ACE in the airway tissue was examined by administering CAP as an intravenous infusion and by an inhaled aerosol. Bronchial reactivity was evaluated by a provocative dose of SP or MCH at a concentration that would double the baseline value of the specific airway resistance (PC200 or PD200). Neither pretreatment with infused CAP (10 mg/kg) nor inhaled CAP (5 mg) enhanced bronchial reactivity to inhaled SP, whereas the reactivity to infused SP (7.5 x 10(-3) to 20 nM/kg) was enhanced significantly by pretreatment with infused CAP (10 mg/kg) (p less than 0.05). The infusion of CAP (10 mg/kg) also enhanced the bronchial reactivity to both infused MCH (0.05 to 25 micrograms/kg) and inhaled MCH (0.05 to 25 mg/ml) (both p less than 0.05). However, the inhalation of CAP (5 mg) did not affect the bronchial reactivity to inhaled MCH. These observations suggest that ACE located on the vascular endothelium may modulate bronchial reactivity.
authors.affiliation: First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Okubo
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology
chemical_list: D016210:Methacholine Chloride; D013373:Substance P; D002216:Captopril; D007703:Peptidyl-Dipeptidase A