[Effects of oral hypoglycemic agents, gliclazide and tolbutamide, on the cardiovascular system (author's transl)].
Recent clinical studies have suggested an association of tolbutamide (TB) therapy with an increased incidence of cardiovascular deaths. In this study, the effects of a newly synthetized hypoglycemic agent, gliclazide (GC), on the cardiovascular system were investigated, and compared with those of TB. Results are as follows: GC was found to be about ten times as active as TB in decreasing blood glucose in rabbits. GC and TB produced a dose-dependent increase in blood pressure and little change in heart rate in rats and rabbits. In driven left rat and rabbit atria, these agents produced a positive inotropic effect. The positive inotropic effects of these drugs were not altered by pretreatment with propranolol, or theophylline. These agents produced little change in the rate in spontaneous beating rat, rabbit and guinea pig atria. Higher doses produced a slightly negative chronotropic response. Neither agent potentiated the intropic effects of isoproterenol on the rabbit and guinea pig left atria. In isolated perfused working rabbit hearts, these compounds produced a slight decrease in coronary flow. It is concluded that GC and TB possess positive inotropic effects on isolated atria, and these effects are not mediated either through adrenergic mechanisms or the cyclic AMP system.
D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005907:Gliclazide / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology*
D001786:Blood Glucose; D013453:Sulfonylurea Compounds; D014044:Tolbutamide; D005907:Gliclazide