Decreased myocardial calcium uptake after isoproterenol in streptozotocin-induced diabetic rats. Studies in the in vitro perfused heart.
Myocardial calcium uptake in response to isoproterenol (ISO, 10(-4) M) was investigated in control and streptozotocin-induced diabetic rats using an in vitro heart perfusion model. An initial labeling with 45Ca added to the perfusate (with or without ISO) was followed by a cold calcium-free washout, thus clearing the myocardial interstitium of 45Ca. In this way the remaining 45Ca was an estimate of the myocardial calcium uptake during the labeling period. In control rats ISO induced a statistically significant increase in myocardial calcium uptake within the first 5 minutes, as well as from the 5th to the 15th minutes after exposure to this strong beta-receptor agonist. In contrast to this, diabetic hearts showed no increase in calcium uptake during any of these periods. The toxic effect of ISO was expressed by a leak of creatinine phosphokinase to the perfusate. In control rats the concentration of creatinine phosphokinase increased after ISO with a statistically significant correlation to the calcium uptake, whereas no enzymatic leak was seen after perfusion of the diabetic hearts. This abnormal response to strong beta-receptor stimulation in experimental diabetes is in accordance with our earlier in vivo finding of a myocardial protection against toxic doses of ISO. These results indicate a decreased catacholamine-induced calcium transport through the myocardial sarcolemma in streptozotocin-induced diabetic rats. This might hypothetically have relevance for diabetic heart disease as well as diabetic neuropathy.
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D013311:Streptozocin; D000242:Cyclic AMP; D003402:Creatine Kinase; D007545:Isoproterenol; D002118:Calcium