Nifedipine inhibits the hypoxia-induced decrease in plasma renin activity in conscious dogs.
Acute hypoxia induces a decrease in plasma renin activity (PRA), mediated, e.g., by an increase in adenosine concentration, calcium channel activity, or inhibition of ATP-sensitive potassium channels. The decrease in PRA results in a decrease in angiotensin II (AngII) and plasma aldosterone concentration (PAC). This study investigates whether these hypoxia-induced mechanisms can be inhibited by the L-type voltage-dependent calcium channel antagonist nifedipine. Eight conscious, chronically tracheotomized dogs received a low sodium diet (0.5 mmol Na x kg body wt(-1) x day(-1)). The dogs were studied twice in randomized order, either with nifedipine infusion (1.5 microg x kg body wt(-1) x min(-1), Nifedipine) or without (Control). The dogs were breathing spontaneously: first hour, normoxia [inspiratory oxygen fraction (FiO2)=0.21]; second and third hour hypoxia (FiO2=0.1). In Controls, PRA (6.8+/-0.8 vs. 3.0+/-0.5 ngAngI x ml(-1) x min(-1)), AngII (13.3+/-1.9 vs. 7.3+/-1.9 pg/ml), and PAC (316+/-50 vs. 69+/-12 pg/ml) decreased during hypoxia (P<0.05). In Nifedipine experiments, PRA (6.5+/-0.9 vs. 10.5+/-2.4 ngAngI x ml(-1) x min(-1)) and AngII (14+/-1.1 vs. 18+/-3.9 pg/ml) increased during hypoxia, whereas the decrease in PAC (292+/-81 vs. 153+/-41 pg/ml) was blunted (P<0.05). These results foster the idea that the hypoxia-induced decrease in PRA involves L-type calcium channel activity.
Höhne
C
C
Experimental Anesthesia, Clinic of Anesthesiology and Surgical Intensive Care Medicine, Campus Virchow-Klinikum, Charité, Berlin, Germany. claudia.hoehne@charite.de
Arntz
E
E
Krebs
M O
MO
Boemke
W
W
Kaczmarczyk
G
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000502:physiology; D003243:Consciousness / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000097:blood* / Q000188:drug therapy; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D012083:Renin / Q000097:blood*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012083:Renin; D009543:Nifedipine