The role of endothelin-1 in strain-related susceptibility to develop hypoxic pulmonary hypertension in rats.
The Hilltop (H) strain compared to the Madison (M) strain of Sprague-Dawley rats develops severe pulmonary hypertension in response to chronic hypoxia. We tested the hypothesis that endothelin-1 (ET-1) contributes to these strain-related differences. Plasma ET-1 content was not modified by chronic hypoxia in either strain. The lung ET-1 peptide and preproET-1 mRNA content were significantly increased to the same magnitude in both strains at 2 and 3 weeks of hypoxia. The ET(A) receptor mRNA increased more at 3 weeks of hypoxia in the lungs of H rats than in M rats, but not at other time points. The ET(B) receptor mRNA was not modified by hypoxia in either strain. After 3 days of normoxic recovery following 2 weeks of hypoxia, ET-1 protein and mRNA levels decreased to baseline levels in both rat strains. We conclude that ET-1 does not contribute to the development of cardiopulmonary differences between the H and M strains in response to hypoxia.
Karamsetty
M R
MR
Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, RI 02903, USA.
Pietras
L
L
Klinger
J R
JR
Lanzillo
J J
JJ
Leiter
J C
JC
Ou
L C
LC
Hill
N S
NS
D000818:Animals; D002908:Chronic Disease; D019332:Endothelin-1 / Q000502:physiology*; D016232:Endothelins / Q000096:biosynthesis; D020022:Genetic Predisposition to Disease; D006400:Hematocrit; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D015151:Immunoblotting; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D016276:Ventricular Function
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D015347:RNA Probes; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin