The effects of candesartan and ramipril on adrenal catecholamine release in anaesthetized dogs.
We have investigated the effects of the angiotensin II type 1 receptor antagonist candesartan, and the angiotensin II converting enzyme inhibitor ramipril, on catecholamine release from the anaesthetized dog's adrenal gland. These drugs were given systemically in low and high doses. The gland was stimulated electrically (0.5-12 Hz) and by angiotensin II infusion (40 ng/kg/min). Electrical stimulation resulted in frequency-dependent increases in catecholamine release. Candesartan (0.8, 4.0 mg/kg) and ramipril (0.125, 0.625 mg/kg) increased basal catecholamine release along with decreases in blood pressure. Both drugs diminished direct nerve stimulation-induced catecholamine release. When both drugs were combined, their inhibitory effect was slightly enhanced. Candesartan blocked catecholamine release induced by angiotensin II. Ramipril was not tested in this respect. The percentage of noradrenaline released during electrical stimulation of the gland remained constant and ranged from 14% to 22%. Both drugs appear to act by blocking local modulation of catecholamine release by the chromaffin cells.
Critchley
Lester
L
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. hcritchley@cuhk.edu.hk
Ding
Baoguo
B
Fok
Benny
B
Wang
Deqing
D
Tomlinson
Brian
B
James
Anthony
A
Thomas
G Neil
GN
Critchley
Julian
J
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003714:Denervation; D004285:Dogs; D004558:Electric Stimulation; D006706:Homeostasis / Q000502:physiology; D008297:Male; D017257:Ramipril / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002395:Catecholamines; D013777:Tetrazoles; D000804:Angiotensin II; D017257:Ramipril; C081643:candesartan