Comparative Study of Protective Effects of Salbutamol and Beclomethasone against Insulin Induced Airway Hyper-reactivity on Isolated Tracheal Smooth Muscle of Guinea Pig.

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin (10(-7) to 10(-3) M), insulin pretreated with fixed concentration of salbutamol (10(-7) M) and beclomethasone (10(-6) M) were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean ± SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 ± 1.13 mm, 14.55 ± 0.62 mm and 22 ± 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction.

A comparative study of the beneficial effects of ipratropium and beclomethasone against insulin-induced tracheal tissue contraction in a guinea pig model.

OBJECTIVE: To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model. MATERIALS AND METHODS: The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin (10(-7) to 10(-3)M) and insulin pretreated with a fixed concentration of beclomethasone (10(-6)M) and ipratropium (10(-6)M) on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph. RESULTS: The means ± standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 ± 1.13, 22 ± 1.15 and 27.8 ± 1.27 mm, respectively. CONCLUSION: The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction.

Acute effect of insulin on guinea pig airways and its amelioration by pre-treatment with salbutamol.

OBJECTIVE: To study the magnitude of insulin-mediated airway hyper-reactivity and to explore the protective effects of salbutamol in inhibiting the insulin-induced airway hyper-responsiveness on tracheal smooth muscle of guinea pigs in vitro. METHODS: The quasi-experimental study was conducted at the Pharmacology Department of Army Medical College, Rawalpindi, in collaboration with the Centre for Research in Experimental and Applied Medicine from December 2011 to July 2012. It used 18 healthy Dunkin Hartely guinea pigs of either gender. Effects of increasing concentrations of histamine (10-8-10-3M), insulin (10-8-10-3 M) and insulin pre-treated with salbutamol (10-6 M) were observed on isolated tracheal strip of guinea pig in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph. Mean and standard error of mean were calculated. SPSS 16 was used for statistical analysis. RESULTS: Histamine and insulin produced a concentration-dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean of maximum amplitudes of contraction with histamine, insulin and insulin pretreated with salbutamol were 92.5 +/- 1.20 mm, 35 +/- 1.13 mm and 14.55 +/- 0.62 mm respectively. Salbutamol shifted the concentration response curve of insulin to the right and downwards. CONCLUSIONS: Salbutamol significantly reduced the insulin mediated airway hyper-reactivity in guinea pigs, suggesting that pre-treatment of inhaled insulin with salbutamol may have clinical implication in the amelioration of its potential respiratory adverse effects such as bronchoconstriction.