Effects of acid-base imbalance on pulmonary angiotensin-converting enzyme in vivo.
The effects of acid-base balance disturbances on pulmonary endothelial angiotensin-converting enzyme (ACE) were studied in anesthetized mechanically ventilated rabbits. Enzyme function was estimated from [3H]benzoyl-Phe-Ala-Pro ([3H]BPAP) utilization under first-order reaction conditions during a single transpulmonary passage and expressed as 1) substrate metabolism (M), 2) Amax/Km (Amax being equal to the product of enzyme mass and the constant of product formation), and 3) (Amax/Km)/100 ml blood flow. When respiratory acidosis/alkalosis was produced by altering respiratory rate at constant airway pressure, substrate (BPAP) utilization varied proportionally to arterial pH and inversely proportionally to arterial PCO2 (PaCO2) (P less than 0.05). Percent BPAP metabolism (%M) ranged from 92 +/- 3 (respiratory alkalosis) to 85 +/- 3 (normal), 82 +/- 3 (respiratory acidosis), and 78 +/- 2% (severe respiratory acidosis). Amax/Km similarly decreased from 899 +/- 129 to 825 +/- 143, 601 +/- 74, and 450 +/- 34 ml/min, respectively, and (Amax/Km)/100 ml blood flow was reduced from 176 +/- 26 to 131 +/- 22, 111 +/- 12, and 97 +/- 5, respectively. However, when respiratory acidosis/alkalosis was produced by altering both respiratory rate and airway pressure, no changes were observed in either %M, Amax/Km or (Amax/Km)/100 ml blood flow. Similarly metabolic alkalosis or acidosis did not alter M, Amax/Km or (Amax/Km)/100 ml blood flow. These results indicate that pulmonary endothelial ACE function can be affected by acid-base disturbances, probably indirectly through changes in perfused microvascular surface area.
Toivonen
H J
HJ
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Catravas
J D
JD
D000137:Acid-Base Imbalance / Q000201:enzymology* / Q000503:physiopathology; D000142:Acidosis, Respiratory / Q000201:enzymology; D000472:Alkalosis, Respiratory / Q000201:enzymology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D006439:Hemodynamics; D008168:Lung / Q000201:enzymology*; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011652:Pulmonary Circulation; D011817:Rabbits
D009842:Oligopeptides; D002245:Carbon Dioxide; C029689:benzoylphenylalanyl-alanyl-proline; D007703:Peptidyl-Dipeptidase A