Modulation of converting enzyme activity by hypoxia and its physiological effects.
To explore the haemodynamic consequences of the reduction in converting enzyme activity by acute alveolar hypoxia we made sequential haemodynamic observations in seven saline-infused and 12 bradykinin-infused anaesthetized, catheterized dogs. They were ventilated initially with room air and then for 50 minutes with hypoxic gas mixtures. Within two minutes after starting hypoxic ventilation, converting enzyme activity decreased, arterial angiotensin II concentrations dropped, and, in the bradykinin-infused dogs, arterial bradykinin concentrations rose. Both groups of dogs experienced a rise in systemic and pulmonary arterial blood pressure in response to hypoxia, but by different mechanisms. In the saline-infused (control) dogs there was increased systemic (+40%) and pulmonary (+90%) vascular resistance while cardiac output was unchanged or slightly reduced. Bradykinin-infused dogs demonstrated reduced systemic vascular resistance (-40%), no increase in pulmonary vascular resistance and a 100% increase in cardiac output. Return to room air breathing restored converting enzyme activity, releasing high concentrations of angiotensin II. Oxygen tension thus regulates converting enzyme activity and hence the circulating levels of angiotensin II and bradykinin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics; D000860:Hypoxia / Q000201:enzymology*; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin