Evidence that guanylate cyclase is involved in modulating the resting tension and neurally induced contraction of the guinea pig tracheal muscle

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-lmethylxanthine, which promotes cyclic guanosine monophospate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle

Streptozotocin alters pancreatic beta-cell responsiveness to glucose within six hours of injection into rats

A 24-hour glycaemic profile following streptozotocin (80 mg/kg. ip) injection was investigated in fasted rats. The most prominent changes in blood glucose were hyperglycaemia associated with low levels of plasma insulin after two hours followed by hypoglycaemia associated with high levels of plasma insulin after six hours; subsequently hyperglycaemia progressively developed and this was associated with decreasing levels of plasma insulin. Further probing revealed that at two hours after streptozotocin injection, the pancreatic ß-cells could not respond to an oral glucose load while, at six hours after, there was an apparent return of ß-cell responsiveness, but subsequently ß-cell responsiveness was progressively lost and histological examination revealed cellular damage. From these results, it is concluded that within six hours of injection, stretozotocin initiates pancreatic ß-cell damage which leads to the development of diabetes mellitus.

Activation of guanylate cyclase in the guinea-pig trachea reduces contractile responses of the smooth muscle

Guinea-pig tracheal strips were used to investigate whether activation of guanylate cyclase in the trachea can reduce the contractile response of the smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a combination of sodium nitrite and ascorbic acid. These activators inhibited tracheal smooth muscle contractions produced by acetylcholine histamine and electrical field stimulation. However, in the presence of methylene blue, a guanylate cyclase inhibitor, tracheal smooth muscle contractions were not inhibited by the activators. But, in the presence of propranolol, which blocked inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium nitrite/ascorbic acid combination were still capable of inhibiting tracheal smooth muscle contractions. Additionally, methylene blue inhibited tracheal smooth muscle relaxation that was electrically induced. These results suggest that the inhibitory action mediated by activated guanylate cyclase may be a mechanism for regulating tracheal smooth muscle contractile reponses

Demonstration of bioequivalence between ventasol syrup and ventolin syrup in humans and in dogs

Ventasol syrup, a new locally produced salbutamol formulation, was compared with the standard salbutamol formulation, ventolin syrup, for determination of oral bioequivalence in stable asthmatic human subjects and in dogs. On separate occasions, each subject received a single 10 ml oral dose of each formulation containing 4 mg salbutamol. In the human subjects, statistically similar peak plasma concentrations of salbutamol were obtained (196ñ7ng/ml for ventasol syrup and 185ñ6ng/ml for ventolin syrup) 3 hours after oral administration of the formulations. From the ratio of the AUC 0-ý for the formulations (1.04), a relative oral bioavailability of 104 per cent , indicating equivalent total salbutamol output, was also obtained in the human subjects. Similarly, in the dogs, the formulations produced statistically equivalent peak plasma concentrations of salbutamol (259ñ24ng/ml for ventasol syrup and 285ñ29ng/ml for ventolin syrup) 3 hours after oral administration. Also, from the ratio of AUC 0-ý for the formulation (1.02), a relative oral bioavailability of 102 per cent , indicating similar total salbutamol output, was obtained in the dogs. From these results, it is concluded that oral bioequivolence between ventasol syrup and ventolin syrup was demonstrated in human subjects and in dogs.