The role of pulmonary vascular responses to chronic hypoxia in the development of chronic mountain sickness in rats.
A strain of Sprague-Dawley rat obtained from Hilltop Labs, Scottsdale, PA (H rats), develops more severe pulmonary hypertension, right ventricular hypertrophy, and polycythemia than a strain obtained from Madison, WI (M rats), following exposure to simulated high altitude. We sought to determine whether differences in pulmonary vascular responses to chronic hypoxia could explain the differing high altitude susceptibilities of the two strains. Vasoconstrictor responses to hypoxia and angiotensin II were tested in blood perfused lungs isolated from rats of both groups exposed to stimulated high altitude (4 to 5 weeks, 0.5 atm), or from sea level controls. Pressure-flow curves, serving as an index of 'passive' vascular resistance, were also determined in the isolated lungs. Vasoconstrictor responses to hypoxia were blunted in high altitude rats of both the H and M strains compared to sea level controls, and the H sea level rats had blunted vasoconstrictor responses to hypoxia compared to the M sea level rats. Vasoconstrictor responses to angiotensin II were similar among the groups and were unaffected by chronic high altitude exposure. Pressure-flow curves were greater in both high altitude groups than in the sea level groups, and those of the H high altitude rats were slightly greater than those of the M high altitude rats. Thus, differences in vasoconstrictor responses to hypoxia do not explain the greater pulmonary hypertension of H high altitude rats. However, greater 'passive' vascular resistance, probably due to more extensive structural remodeling of pulmonary vessels, does appear to contribute to the greater pulmonary hypertension of the H rats.
D000532:Altitude Sickness / Q000503:physiopathology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D011086:Polycythemia / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II