- © 2003 by the Association of Clinical Scientists, Inc.
Inducible Nitric Oxide Synthase and Heme Oxygenase-1 in Rat Heart: Direct Effect of Chronic Exposure to Hypoxia
- Alfredo Grilli1,
- Maria Anna De Lutiis1,
- Antonia Patruno1,
- Lorenza Speranza1,
- Federico Gizzi1,
- Alfonso A. Taccardi2,
- Pericle Di Napoli2,
- Raffaele De Caterina2,
- Pio Conti3 and
- Mario Felaco1
- 1Departments of Biomorphology, 2Clinical Science and Bioimaging, and 3Oncology and Neurosciences, Faculty of Medicine and Surgery, Università degli Studi “G. d’Annunzio,” Chieti, Italy
- Address correspondence to Professor Mario Felaco, Department of Biomorphology, Faculty of Medicine and Surgery, University G. d’Annunzio, via dei Vestini, Chieti 66013, Italy; tel 39 087 135 55306; fax 39 087 157 4 361; e-mail mfelaco{at}unich.it.
- Received 18 December 2002.
- Accepted 3 January 2003.
Abstract
Hypoxia is a potent regulator of various biological process. Mammalian cells respond to hypoxia by increased expression of several genes. The aim of this study was to evaluate the effects of chronic exposure to low oxygen tension on the induction of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) in rat heart. Male Wistar rats were assigned randomly to 4 groups: (A) control rats maintained in normoxic conditions for 7 and 14 days; (B) rats maintained in hypoxic conditions for 7 and 14 days; (C) rats maintained in normoxic conditions for 7 days and then transferred to hypoxic conditions for 7 days; and (D) rats maintained in hypoxic conditions for 7 days and then transferred to normoxic conditions for 7 days. In Group A, iNOS and HO-1 immunoreactivities were not evident; in Group B these immunoreactivities increased from day 7 to 14; in Group C the immunoreactivities decreased on day 7, compared to day 14; and in Group D, the immunoreactivities increased on day 7, compared to day 14. These findings were confirmed by Western blot analyses of the respective proteins and by rt-PCR assays of the corresponding mRNAs. The results indicate that the adaptive response to hypoxia involves up-regulation of HO-1 through iNOS activation in cardiac cells. HO-1 helps to regulate vascular tone via CO and thereby participates in an important cardiac defense mechanism.
