Hyperoxia-induced converting enzyme insufficiency in conscious rat: cardiovascular effects.
The effects of exposing rats to hyperoxia (100 percent O2) at normal atmospheric pressure for periods of 24-48 hours on components of the renin-angiotensin system and on blood pressure control were examined. Intrapulmonary conversion of angiotensin I (AI) to angiotensin (AII) was assessed using an isolated lung preparation perfused at constant flow. Exposure of rats to hyperoxia for 44-48 hours reduced single pass conversion of AI to AII in the pulmonary circulation from control levels of 82 +/- 4 to 29 +/- 5 percent (p less than 0.001). AII levels in trunk blood of 44-48 hour O2 exposed animals were 5.2 +/- 1.9 pg/ml, compared to 37.9 +/- 10.0 pg/ml in controls (p less than 0.001). Mean arterial pressure decreased significantly from 117 +/- 4.3 to 103 +/- 6.7 mmHg (p less than 0.05) in the O2 exposed group despite a threefold increase in plasma renin activity. The pressor response to exogenous AI was significantly diminished by O2 exposure, while the pressor response to exogenous AII remained unchanged from control. Pulmonary angiotensin-converting enzyme activity fell to approximately 50 percent of control in O2 exposed animals, but circulating converting enzyme activity was not change in this group. None of these alterations was apparent following 24 hours of hyperoxic exposure. These data suggest that O2 induced impairment in activity of angiotensin-converting enzyme at the endothelial membrane level has functionally significant effects on cardiovascular homeostasis, probably via reduced generation of endogenous AII.
D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D008168:Lung / Q000187:drug effects / Q000648:ultrastructure; D001121:Lysine Carboxypeptidase / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D010100:Oxygen / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D012083:Renin; D010100:Oxygen