© 2003 European Society of Cardiology
Role of nitric oxide in posthypoxic contractile dysfunction of diabetic cardiomyopathy
a Department of Cardiology, University of Wales College of Medicine Heath Park, Cardiff CF4 4XN, UK
b Discipline of Surgery, University of Tasmania Hobart, Australia
c Guy's, King's & St. Thomas's School of Medicine, King's College London Bessemer Road, London SE5 9PJ, UK
* Corresponding author. Tel: +44-207-346-3865; fax: +44-207-346-4771. E-mail address: ajay.shah{at}kcl.ac.uk
 |
Abstract |
|---|
We investigated the role of nitric oxide synthase (NOS) in the contractile dysfunction of diabetic cardiomyopathy, comparing streptozotocin-treated (60 mg/kg) diabetic Wistar rats with matched non-diabetic controls. Isolated isovolumic heart function was studied during normoxia and in response to brief hypoxia-reoxygenation. Diabetic hearts had significantly lower left-ventricular pressure and slower isovolumic relaxation than controls (relaxation time constant, T 40.2±2.3 vs. 27.7±0.9 ms; P<0.05) and a blunted response to hypoxia. These abnormalities were unaffected by NOS inhibition. Upon reoxygenation after brief hypoxia, diabetic hearts exhibited substantial worsening of LV relaxation compared to normal hearts (T 69.1±3.3 vs. 56.6±7.9 ms; P<0.05). This post-hypoxic diastolic dysfunction was significantly attenuated either by the non-selective NOS inhibitor L-NAME, the iNOS inhibitor L-NIL, or the reactive-oxygen-species (ROS) scavenger thiourea. Only diabetic hearts expressed iNOS protein, whereas eNOS expression was similar in both groups. In conclusion, diabetic hearts exhibit markedly abnormal post-hypoxic relaxation, which is attributable to both ROS and NO derived from iNOS.
Key Words: Diastole • Nitric oxide synthase (NOS) • Hypoxia • Relaxation • Reactive oxygen species
Received August 16, 2002; Revised October 18, 2002; Accepted November 12, 2002
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. J. Crespo, J. Zalacain, D. C. Dunbar, N. Cruz, and L. Arocho Cardiac Oxidative Stress Is Elevated at the Onset of Dilated Cardiomyopathy in Streptozotocin-Diabetic Rats Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2008; 13(1): 64 - 71. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Jesmin, S. Zaedi, S. Maeda, I. Yamaguchi, K. Goto, and T. Miyauchi Effects of a Selective Endothelin A Receptor Antagonist on the Expressions of iNOS and eNOS in the Heart of Early Streptozotocin-Induced Diabetic Rats. Experimental Biology and Medicine, June 1, 2006; 231(6): 925 - 931. [Abstract] [Full Text] [PDF]
|
|