Buchheit K H, Hofmann A, Fozard J R
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Eur J Pharmacol. 1995 Dec 4;287(1):85-8. doi: 10.1016/0014-2999(95)00613-3.
Guinea pigs were treated for 10 days with (+/-)-salbutamol (0.2 mg/kg/day, delivered from subcutaneously implanted osmotic minipumps). Airway reactivity to intravenously administered histamine, methacholine and bombesin was substantially increased in salbutamol-treated guinea pigs relative to controls. In the same animals, the potency of intravenously administered salbutamol to reverse bombesin-induced bronchoconstriction remained unchanged thus exactly reflecting effects in man. In conclusion, subchronic administration of salbutamol at low doses to guinea pigs increases airway reactivity. Since the bronchorelaxant effect of salbutamol remained unchanged, desensitisation of beta-adrenoceptors on airway smooth muscle is unlikely to account for this effect.
豚鼠用(±)-沙丁胺醇治疗10天(0.2毫克/千克/天,通过皮下植入的渗透微型泵给药)。与对照组相比,沙丁胺醇治疗的豚鼠对静脉注射组胺、乙酰甲胆碱和蛙皮素的气道反应性显著增加。在同一批动物中,静脉注射沙丁胺醇逆转蛙皮素诱导的支气管收缩的效力保持不变,这与在人体中的效应完全相符。总之,对豚鼠低剂量亚慢性给予沙丁胺醇会增加气道反应性。由于沙丁胺醇的支气管舒张作用保持不变,气道平滑肌上β-肾上腺素能受体脱敏不太可能是这种效应的原因。