Inducible nitric oxide synthase and heme oxygenase-1 in rat heart: direct effect of chronic exposure to hypoxia.
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.
Grilli
Alfredo
A
Department of Biomorphology, Faculty of Medicine and Surgery, Università degli Studi G. d'Annunzio, Chieti, Italy.
De Lutiis
Maria Anna
MA
Patruno
Antonia
A
Speranza
Lorenza
L
Gizzi
Federico
F
Taccardi
Alfonso A
AA
Di Napoli
Pericle
P
De Caterina
Raffaele
R
Conti
Pio
P
Felaco
Mario
M
D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D004790:Enzyme Induction; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D000860:Hypoxia / Q000201:enzymology*; D007124:Immunoenzyme Techniques; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D017931:DNA Primers; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1