Evidence of a relationship between coronary endothelial nitric oxide production and oxygen supply.

The aim of this study was to evaluate tissue nitric oxide (NO) production in rat hearts submitted to chronic changes of pO2 by means of exposure to hypoxia (13 days) or hyperoxia (72 hours). Wistar rat (250-300 gr. body weight) were used and subdivided into 3 groups: A) Control hearts; B) Hypoxic hearts; C) Hyperoxic hearts. After chronic hypoxia or hyperoxia, hearts were excised and mounted on working heart apparatus to assess haemodynamic parameters, CPK and purine release in coronary effluent and heart weight changes (myocardial edema). We also evaluated ventricular remodeling, myocytes damage (mitochondrial score, cell swelling) and NO production by means of NADPH-diaphorase (total NO production) and Immunoperoxidase labeled anti-NOS-3 Ab (endothelial NO). Quantitative analysis of histological findings and NO was performed by a computerized image analysis system. In hearts subjected to chronic hypoxia (B group), myocytes ultrastructure was well preserved and associated to a significant (p<0.001 vs A) increase of endothelial NO. In chronic hyperoxic hearts (C group) we observed evident signs of cellular damage (mitochondrial damage, cell swelling); NO production (endothelial and total NO) was significantly (p<0.01 vs A) reduced. Data show that in rat heart endothelial NO production is strictly related to oxygen supply.