Blood glucose was constantly monitored (Ames glucome-ter, Miles Lab, Kyoto Daiichi, Kyoto, Japan) and, if it was considered necessary to counteract the hypoglycemic effect ofthe higher doses of the drugs, glucose was administered intravenously (0 to 5.5 mmol/kg) 5 mins before drug administration. At the end of the experiments serum potassium level was also determined.Data were evaluated by multiple t test and regression analysis.
It is well known that vagal stimulation induces considerable depression of the heart rate and a slight decrease in mean arterial blood pressure.
Comparison of the effects of the different hypoglycemic sulphonylureas showed that glibenclamide stimulated the heart rate depression induced by vagal stimulation (Figure 1) with enhanced frequency, in a dose-dependent fashion. The other investigated compounds did not affect or even counteract the alterations of heart rate due to parasympathetic stimuli.
The decrease in blood pressure caused by electrical stimulation of the vagal nerve with increasing frequency was potentiated by glibenclamide, glimepiride and glipizide depending on their doses. However, this decrease in blood pressure was not influenced or counteracted by chlorpropamide, carbutamide, tolbutamide and gliclazide . Basal values, serum glucose or potassium levels could not provide any explanation for these differences (Table 1).
Figure 1 Effects ofsulphonylureas on percentage alterations in heart rate induced by electrical stimulation ofthe vagal nerve in dogs. The effect of stimulation with increasing frequency on the heart rate is projected in the frontal plane, while that of the selected doses of sulphonylureas is projected in the lateral plane, resulting in the stereoscopic illustration. Differences (mean ± SEM) are compared with solvent You can finally spend less money and time whenever your need since you are being given access to the best online pharmacy you have ever come across.
TABLE 1 Hemodynamic and metabolic variables of study animals assigned to the different treatment groups (n=6 in each group)
|Body weight (kg)||10.6+1.5||12.17+1.2||12.5+1.7||13+1||11.8+1.5||10.9+1.5||10.2+1.3|
|Mean arterial blood pressure (kPa)||17.56±2.70||18.22+0.66||17.80+0.89||17.33+1.14||15.70+1.40||19.06+0.77||19.5+0.99|
|Heart rate (beats/min)||191 ±14||179.3+9||177+11||181+7||171+12||167+15||171+12|
|Blood glucose (mmol/L)||5.9+1.1||6.19±0.9||5.68+1.22||4.95+1.4||5.73+0.8||5.3+1.05||5.4+1.05|
|Serum potassium (mmol/L)||4.2+0.5||4.4+0.6||4.1+0.3||4.6+0.5||4.3+0.50||4.1+0.5||