Regulation of the angiotensin-converting enzyme activity by a time-course hypoxia in the carotid body.
Chronic hypoxia activates a local angiotensin-generating system in the carotid body. Here, we test the hypothesis that the activity of the critical enzyme for this system, angiotensin-converting enzyme (ACE), in the carotid body is subject to regulation by a time-course hypoxia. Results from the carotid body assays showed that ACE activity was markedly increased under the hypoxic stress of 7-, 14-, 21-, and 28-day exposures. The changes in ACE activity of 7-day (15.00 vs. 30.95 x 10(-5) nmol.microg(-1).min(-1)), 14-day (8.73 vs. 30.25 x 10(-5) nmol.microg(-1).min(-1)), and 21-day (11.41 vs. 31.83 x 10(-5) nmol.microg(-1).min(-1)) hypoxia treatments were enhanced significantly. However, ACE activity in 28-day (13.18 vs. 24.53 x 10(-5) nmol.microg(-1).min(-1)) hypoxia treatment was observed to increase insignificantly when compared with results in the respective control groups. Captopril inhibited all rises in ACE activity in both the control and experimental groups. Results clearly indicate an activation of the enzymatic activity of ACE, the critical enzyme for determining the conversion of angiotensin I into the physiologically active angiotensin II, by chronic hypoxia in the carotid body. An increase in the ACE activity may increase the local production of angiotensin II in the carotid body and thus its agonist action at the AT1 receptor. This may be important in the modulation of cardiopulmonary adaptation in the hypoxic ventilatory response as well as for electrolyte and water homeostasis during chronic hypoxia.
Lam
Siu Yin
SY
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Fung
Man-Lung
ML
Leung
Po Sing
PS
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005453:Fluorescence; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A