Airways hyperreactivity and bronchoconstriction induced by vanadate in the guinea‐pig

• Published in: British journal of pharmacology 1987-09, Vol.92 (1), p.173-180
• Main Authors: Nayler, Ross A., Mitchell, Howard W.
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Aerosols; Animals; Atropine - pharmacology; Biological and medical sciences; Bronchi - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Female; Guinea Pigs; Histamine - pharmacology; Infusions, Intravenous; Male; Medical sciences; Metals and various inorganic compounds; Propranolol - pharmacology; Reflex - drug effects; Serotonin - pharmacology; Toxicology; Vagotomy; Vanadates - administration & dosage; Vanadates - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1987.tb11309.x

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 < 0.05, n = 6) but caused no change in Raw. 3 Histamine (3 μg 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 < 0.02, n = 3). 4 Bronchoconstrictor responses to acetylcholine (6 μg kg−1 i.v.) and 5‐hydroxytryptamine (6 μg 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 μg kg−1 i.v.) caused a transient tachypnoea which was also enhanced by vanadate (0.3–3 mg kg−1 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.