Inhibition of Nitric Oxide Synthase by -NAME Improves Ventricular Performance in Streptozotocin- diabetic Rats

The overall goal of this study was to determine if activation of the nitric oxide synthetic pathway suppressed basal ventricular performance and the responsiveness toβ-adrenergic stimulation characteristic of cardiac function in the 8-week streptozotocin (60 mg/kg, i.v.) diabetic (STZ-Db) rat. Left ventricular performance was measured in isolated working hearts, before and at the peak response to 0.8μm dobutamine, in the absence or presence of NG-nitro- -arginine methyl ester ( -NAME, 1 m ), a non-selective inhibitor of nitric oxide synthase (NOS). Ventricular performance was suppressed in the STZ-Db heart under basal (decreased heart rate, cardiac output, aortic flow −dP/dt) and dobutamine-stimulated (diminished rise in +dP/dtand maximum systolic pressure) conditions. -NAME had minimal effects on basal or dobutamine-stimulated ventricular performance in control hearts. In contrast, -NAME infusion in hearts from STZ-Db returned the depressed heart rate to control values, which was correlated with an increase in aortic flow. In addition, the dobutamine-stimulated rise in maximum systolic pressure and +dP/dtwere similar in the control and STZ-Db rats in the presence of -NAME. Western blot analysis detected the presence of inducible nitric oxide synthase (NOS) and a significant (P<0.001) increase in the constitutive NOS in ventricular myocytes from STZ-Db rats. These data suggest that an increased production of nitric oxide by NOS in ventricular myocytes from STZ-Db animals suppressed basal ventricular performance and the responsiveness toβ-adrenergic stimulation in diabetic hearts.