Nayler R A, Mitchell H W
Department of Physiology, University of Western Australia, Nedlands.
Br J Pharmacol. 1987 Sep;92(1):173-80. 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 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.
1 通过测量气道阻力（Raw）和动态肺顺应性（Cdyn），在自主呼吸的麻醉豚鼠中观察钒酸盐诱导的支气管收缩和气道高反应性的特征。钒酸盐（0.3 - 3 mg kg⁻¹静脉注射，持续25分钟）以可逆的、剂量相关的方式增加Raw并降低Cdyn。这种作用（1 mg kg⁻¹钒酸盐）不受阿托品（1 mg kg⁻¹静脉注射）、普萘洛尔（1 mg kg⁻¹静脉注射）或双侧迷走神经切断术的抑制，提示对气道平滑肌有直接作用。2 雾化吸入钒酸盐（10% w/v于水中）3分钟使Cdyn降低19.5%（P < 0.05，n = 6），但对Raw无影响。3 组胺（3 μg kg⁻¹静脉注射）引起支气管收缩，钒酸盐以剂量相关的方式增强这种收缩。这种高反应性（在1 mg kg⁻¹静脉注射钒酸盐后）在普萘洛尔或双侧迷走神经切断术后无变化，但部分被阿托品阻断（钒酸盐对组胺引起的Cdyn变化的增强作用减弱，P < 0.02，n = 3）。4 对乙酰胆碱（6 μg kg⁻¹静脉注射）和5 - 羟色胺（6 μg kg⁻¹静脉注射）的支气管收缩反应也被钒酸盐（1 mg kg⁻¹静脉注射）增强。钒酸盐给药后对三种测试支气管收缩剂的高反应性在钒酸盐输注期间持续存在，并在输注停止后45分钟逆转。5 组胺（3 μg kg⁻¹静脉注射）引起短暂的呼吸急促，钒酸盐（0.3 - 3 mg kg⁻¹静脉注射）也以剂量相关的方式增强这种呼吸急促，与气道反应性增加相关（r = 0.66，n = 11）。6 结论是，钒酸盐诱导的气道高反应性起源于非迷走神经（传出）且在很大程度上是非胆碱能的，似乎涉及钒酸盐在肺本身内的作用。
