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

• Published in: Journal of molecular and cellular cardiology 1997-09, Vol.29 (9), p.2393-2402
• Main Authors: Smith, Jacquelyn M., Paulson, Dennis J., Romano, Fred D.
• Format: Article
• Language: English
• Subjects: cNOS; Dobutamine; iNOS; l-NAME; Myocardial contractility; Myocytes; Nitric oxide; Streptozotocin-diabetic rat; β -adrenergic agonists
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1997.0474

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-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/dtand 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/dtwere similar in the control and STZ-Db rats in the presence ofl-NAME. Western blot analysis detected the presence of inducible nitric oxide synthase (NOS) and a significant (P