Airways hyperreactivity and bronchoconstriction induced by vanadate in the guinea-pig.
1 The characteristics of vanadate-induced bronchoconstriction and airways hyperreactivity were observed in spontaneously breathing anaesthetized guinea-pigs by measurement of airways resistance (Raw) and dynamic lung compliance (Cdyn). Vanadate (0.3-3 mg kg-1 i.v. over 25 min) increased Raw and decreased Cdyn in a reversible, dose-related manner. This action (1 mg kg-1 vanadate) was not inhibited by atropine (1 mg kg-1 i.v.), propranolol (1 mg kg-1 i.v.) or bilateral vagotomy, suggesting a direct effect on the airways smooth muscle. 2 An aerosol of vanadate (10% w/v in H2O) for 3 min decreased Cdyn by 19.5% (P less than 0.05, n = 6) but caused no change in Raw. 3 Histamine (3 micrograms kg-1 i.v.) caused a bronchoconstriction which was enhanced by vanadate in a dose-related manner. This hyperreactivity (after 1 mg kg-1 i.v. vanadate) was unchanged after propranolol or bilateral vagotomy, but was partly blocked by atropine (enhancement by vanadate of the Cdyn change to histamine was diminished, P less than 0.02, n = 3). 4 Bronchoconstrictor responses to acetylcholine (6 micrograms kg-1 i.v.) and 5-hydroxytryptamine (6 micrograms kg-1 i.v.) were also enhanced by vanadate (1 mg kg-1 i.v.) Hyperreactivity after vanadate to the three bronchoconstrictors tested continued during vanadate infusion and was reversed 45 min after cessation of infusion. 5 Histamine (3 ;Lgkg-' i.v.) caused a transient tachypnoea which was also enhanced by vanadate (0.3-3mgkg-'i.v.), in a dose-related manner, in association with the increased reactivity of the airways (r = 0.66, n = 11). 6 It is concluded that vanadate-induced airways hyperreactivity is non-vagal (efferent) and largely non-cholinergic in origin and appears to involve an action of vanadate within the lung itself.
Nayler
R A
RA
Department of Physiology, University of Western Australia, Nedlands.
Mitchell
H W
HW
D000109:Acetylcholine / Q000494:pharmacology; D000336:Aerosols; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D014628:Vagotomy; D014638:Vanadates / Q000008:administration & dosage / Q000494:pharmacology*
D000336:Aerosols; D012701:Serotonin; D014638:Vanadates; D001285:Atropine; D006632:Histamine; D011433:Propranolol; D000109:Acetylcholine