Effect of hypoxia on the conversion of angiotensin I to II in cultured porcine pulmonary endothelial cells.
Earlier studies by other investigators have shown that acute exposure of cultured endothelial cells to hypoxic atmospheres inhibits the activity of the angiotensin converting enzyme in situ, resulting in severe but reversible depression of the rate of degradation of bradykinin. We exposed primary cultures of endothelial cells from the pulmonary artery of the pig to a range of hypoxic gas mixtures and measured the activity of the angiotensin converting enzyme in situ using angiotensin I as substrate. Each cell flask was exposed in random sequence to both hypoxic gas mixtures (PO2 29-69 torr) and room air for 40 min in Dulbecco's medium containing angiotensin I at concentrations of 1000 (N = 7), 500 (N = 8) or 100 ng/ml (N = 4). Angiotensin I disappearance rates and angiotensin II generation rates were linear. Recovery of immunoreactive peptide as either angiotensin I or II following 40 min of incubation was 86 +/- 17% (S.D.). The rate of increase in angiotensin II concentration in surface medium in room air experiments was 91 +/- 51 (S.D.) ng x ml-1 x hr-1. During hypoxia it was 85 +/- 42 ng x ml-1 x hr-1. The difference in rates was not significant by paired t analysis. The results of this study are consistent with earlier observations by the authors which suggest that hypoxia-induced depression of angiotensin I conversion in vivo is due to hemodynamic phenomena. Further studies are needed to clarify the role of cellular mechanisms in hypoxia-induced depression of angiotensin metabolism.
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism; D007700:Kinetics; D010100:Oxygen / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism*; D013552:Swine
D000809:Angiotensins; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D010100:Oxygen