Inhibition of nitric oxide synthase enhances contractile response of ventricular myocytes from streptozotocin-diabetic rats
The magnitude and kinetics of the L-type calcium current were compared in single left ventricular myocytes isolated from 8-mo-old (8M) and 19-mo-old (19M) genetically diabetic rats (WBN/Kob rats) and age-matched control rats. A diabetic state occurred at 19M but not at 8M. The left ventricular contractility was reduced in 19M WBN/Kob rats compared with age-matched control rats. The duration of the action potential was longer in 19M WBN/Kob rats than in the age-matched control rats. Peak inward current density was similar between diabetic rats and age-matched control rats. In addition, aging did not affect the current density at 8M or 19M. The various kinetic parameters of the L-type calcium current were not different between 19M diabetic and control cell types. The percent increase in the amplitude of the calcium current induced by isoproterenol was less in diabetic cells at the age of 19M, but not at the age of 8M, compared with age-matched control cells. Forskolin (10(-5) M), intracellularly applied adenosine 3',5'-cyclic monophosphate (5 x 10(-5) M), and guanosine 5'-[gamma-thio]triphosphate (10(-4) M) were equally effective in increasing the current in 19M diabetic and age-matched control cell types. The present study demonstrates that the basal calcium current density and kinetic parameters of the current were not altered. However, a decrease in response to beta-stimulation occurred in genetically diabetic rats compared with control rats.