Inhibition of nitric oxide synthase by L-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 to beta-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 0.8 microM dobutamine, in the absence or presence of NG-nitro-L-arginine methyl ester (L-NAME, 1 mM), 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/dt and maximum systolic pressure) conditions. L-NAME had minimal effects on basal or dobutamine-stimulated ventricular performance in control hearts. In contrast, L-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/dt were similar in the control and STZ-Db rats in the presence of l-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 to beta-adrenergic stimulation in diabetic hearts.

Smith JM ，Paulson DJ ，Romano FD 《JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY》

Pioglitazone, a PPARgamma agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats.

Majithiya JB ，Paramar AN ，Balaraman R 《CARDIOVASCULAR RESEARCH》

Inhibition of beta- but not alpha 1-mediated adrenergic responses in isolated hearts and cardiomyocytes by nitric oxide and 8-bromo cyclic GMP.

Ebihara Y ，Karmazyn M 《CARDIOVASCULAR RESEARCH》

Selective modulation of endogenous nitric oxide formation in ischemia/reperfusion injury in isolated rat hearts--effects on regional myocardial flow and enzyme release.

Han H ，Kaiser R ，Hu K ，Laser M ，Ertl G ，Bauersachs J ... -  《BASIC RESEARCH IN CARDIOLOGY》

Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

Amour J ，Loyer X ，Le Guen M ，Mabrouk N ，David JS ，Camors E ，Carusio N ，Vivien B ，Andriantsitohaina R ，Heymes C ，Riou B ... -  《ANESTHESIOLOGY》