EFFECTS OF ACETALDEHYDE ON THE ISOLATED PAPILLARY-MUSCLE OF DIABETIC RATS

The effects of acetaldehyde (ACA) were examined in isolated electrical ly driven papillary muscle preparations from normal and streptozotocin -treated diabetic rats, Muscles from diabetic rats developed greater t ension than those from normal rats. In muscles from both groups, ACA c aused concentration-dependent negative inotropic effects that were ind ependent of cholinergic or purinergic mechanisms and were not attribut able to nitric oxide (NO) release. ACA was three to five times more po tent with regard to its negative inotropic effect in diabetic than in normal rat muscles. A propranolol-sensitive, sympathetically mediated positive inotropic effect occurred at certain concentrations. Decreasi ng [Ca2+], from 2.7 to 0.5 mM reduced basal developed force to a signi ficantly greater extent in muscles from normal rats than in those from diabetic rats. In low [Ca2+](o), concentration-response curves to CaC l2 in diabetic muscles were displaced to the left of that in normal mu scles, suggesting that diabetic muscles are more sensitive to the posi tive inotropic effect of added CaCl2 at low [Ca2+](o), whereas at high er [Ca2+](o) (>1 mM), normal muscles developed more force in response to added CaCl2. ACA 10 and 30 mM more readily inhibited CaCl2-induced positive inotropic effect in normal than in diabetic muscles. Force-fr equency curves, (negative staircase response) were recorded in both no rmal and diabetic muscles. In diabetic muscles, the curve exhibited a positive component at the lowest frequencies applied and was displaced to the right of that in normal muscle. ACA concentration-dependently inhibited force development, and diabetic muscles were more susceptibl e to the negative inotropic effect of ACA, when the stimulation freque ncy was increased. Ouabain 30 mu M induced a positive inotropic effect of 21% in normal rat muscles, but increased basal developed force by 7% in diabetic preparations (p < 0.01). The magnitude of the negative inotropic effect of ACA with or without ouabain were similar in papill ary muscles from both groups. In the diabetic myocardium, in which res ting intracellular Ca2+ levels reportedly are increased, the negative inotropic effect of ACA is attenuated by increasing the [Ca2+](o), but not by increasing the [Ca2+](i) with ouabain. The mechanism(s) involv ed in the negative inotropic effect of ACA are intimately related to t he intracellular Ca2+ levels, which may not be identical in normal and diabetic myocardium, and that ACA reduces contractility by preventing the release of activator Ca2+.