Altered angiotensin-converting enzyme in lung and extrapulmonary tissues of hypoxia-adapted rats.
The effects of exposing rats to hypoxia (10% O2) at normal atmospheric pressure for periods of 14 or 28 days on angiotensin-converting enzyme (ACE) activity and stores of angiotensin I (ANG I) and angiotensin II (ANG II) in lung, kidney, brain, and testis were examined. ACE activity was measured by spectrophotometric assay, and active sites of ACE were estimated by measuring the binding of 125I-351A [N-(1-carbonyl-3-phenyl-propyl)-L-lysyl-L-proline], a highly specific active site-directed inhibitor of ACE, to tissue homogenates and perfused lungs. Hypoxia exposure produced progressive reductions in ACE activity in lung homogenates and in ACE inhibitor binding to perfused lungs. ANG II levels in lungs from hypoxia-adapted animals were significantly less than air controls, suggesting that the reduction in intrapulmonary ACE activity was associated with reduced local generation of ANG II. ACE activity was increased in kidney and unchanged in brain and testis of hypoxia-adapted rats compared with air controls. Thus the effects of chronic hypoxia on catalytically active ACE and ACE active sites in the intact animal were organ specific. Adaptation to chronic hypoxia did not significantly alter plasma renin activity or ANG I or ANG II levels or serum ACE content. The hypoxia-induced alterations in lung and kidney ACE were reversible after return to a normoxic environment.
Oparil
S
S
Department of Medicine, University of Alabama, Birmingham 35294.
Narkates
A J
AJ
Jackson
R M
RM
Ann
H S
HS
D000222:Adaptation, Physiological; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000201:enzymology / Q000503:physiopathology*; D017706:Lisinopril; D008168:Lung / Q000201:enzymology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004151:Dipeptides; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A