Effect of chronic diuretics on epinephrine-induced ventricular arrhythmias: a comparison of hydrochlorothiazide and amiloride in the rat.
The purpose of this study was to determine if chronic administration of the diuretics hydrochlorothiazide and amiloride alters the response to catecholamine-induced ventricular arrhythmias. The protocol consisted of four groups of Wistar rats. Group I, or control group, received daily subcutaneous injections of saline; group II received hydrochlorothiazide, 100 mg/kg/day s.c.; group III received amiloride, 0.5 or 1.0 mg/kg/day s.c.; and group IV received amiloride, 0.5 mg/kg/day, plus hydrochlorothiazide, 100 mg/kg/day. The treatment period lasted 18 days. After completion of the treatment period, under pentobarbital anesthesia, epinephrine was infused and the electrocardiogram and blood pressure recorded. Hydrochlorothiazide produced a significant (p less than 0.05) leftward shift in the dose-response relationship, that is, a smaller epinephrine concentration produced earlier onset of ventricular arrhythmias and mortality from fatal ventricular arrhythmias. Amiloride, at the higher dose, significantly (p less than 0.05) shifted to the right the dose-response relationship between epinephrine and occurrence of arrhythmias--i.e., a larger epinephrine dose was necessary to produce the same amount of arrhythmias. There were no significant differences in heart rate or blood pressure responses to epinephrine among the four groups. Serum and myocardial electrolytes were measured in a separate group of rats that did not receive epinephrine. There were no significant differences among groups for myocardial electrolytes. After hydrochlorothiazide administration, serum calcium and magnesium were decreased and bicarbonate was increased compared with the control group. In the amiloride group, only serum sodium was significantly changed, being slightly increased. This suggests that serum electrolyte levels may account for the effects of hydrochlorothiazide but do not account for the effect of amiloride.
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004573:Electrolytes / Q000097:blood / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004232:Diuretics; D004573:Electrolytes; D006852:Hydrochlorothiazide; D000584:Amiloride; D004837:Epinephrine