ACUTE-HYPOXIA UP-REGULATES NOS GENE-EXPRESSION IN RATS

This study aimed to investigate the influence of acute tissue hypoxyge nation on the expression of NO synthase (NOS) genes in vivo. To this e nd, male Sprague-Dawley rats were exposed either to 9% oxygen or to 0. 1% carbon monoxide for 6 h, and mRNA levels of NOS-I, -II, and -III in kidneys, livers, lungs, and left and right heart ventricles were assa yed by ribonuclease protection. For comparison, mRNA levels of erythro poietin were also measured in these tissues. NOS-III mRNA was highly a bundant in all organs investigated. NOS-II mRNA was detected in lungs and hearts but not in kidneys and livers. NOS-I mRNA was found in kidn eys, lungs, and hearts but not in livers. NOS-III mRNA levels were upr egulated by hypoxia in all tissues examined, with the least effect (1. 2-fold) in the left ventricle and the greatest effect (2.6-fold) in th e lung. NOS-II mRNA was substantially downregulated in the ventricles by both treatments but not changed in the lung. NOS-I mRNA was upregul ated by carbon monoxide in kidneys and lungs and by 9% oxygen in the l ung. These findings suggest that NOS-III and possibly also NOS-I gene expression behave like oxygen-regulated genes, whereas the general eff ect of tissue hypoxygenation on NOS-II gene expression is less clear. Because NOS-III is primarily expressed in endothelial cells, a general upregulation of NOS in these cells may be of relevance for the regula tion and maintenance of blood flow through hypoxic tissues.