J Korean Soc Hypertens.  2014 Jun;20(2):51-67. 10.5646/jksh.2014.20.2.51.

Comparison of Inhibitory Effects between Enalapril and Losartan on Adrenal Catecholamine Secretion

Affiliations
  • 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Korea.
  • 2Department of Internal Medicine, Chosun University School of Medicine, Gwangju, Korea.
  • 3Department of Pharmacology, Chosun University School of Medicine, Gwangju, Korea. dylim@chosun.ac.kr

Abstract

BACKGROUND
The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor with losartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland.
METHODS
The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer.
RESULTS
Both enalapril and losartan during perfusion into an adrenal vein for 90 minutes inhibited the CA release evoked by acetylcholine (ACh), 1.1-dimethyl-4-phenyl piperazinium (DMPP, a selective Nn agonist), high K+ (a direct membrane-depolarizer), 3-(m-chloro-phenyl-carbamoyl-oxy-2-butynyl-trimethyl ammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence of enalapril or losartan, the CA release evoked by veratridine (an activator of voltage-dependent Na+ channels), 6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate (BAY-K-8644, an L-type Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly reduced. Based on the same concentration of enalapril and losartan, for the CA release evoked by ACh, high K+, DMPP, McN-A-343, Ang II, veratridine, BAY-K-8644, and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: losartan > enalapril. In the simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared with that of enalapril- or losartan-treated alone.
CONCLUSIONS
Collectively, these results demonstrate that both enalapril and losartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in the perfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seems to be more potent than that of enalapril.

Keyword

Enalapril; Losartan; Catecholamine secretion; Adrenal medulla; angiotensin II type-1 receptor blocker; Angiotensin-converting enzyme inhibitor

MeSH Terms

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Acetylcholine
Adrenal Glands
Adrenal Medulla
Ammonium Compounds
Angiotensin II
Animals
Catecholamines
Cytoplasm
Dimethylphenylpiperazinium Iodide
Enalapril*
Losartan*
Perfusion
Rats
Veins
Veratridine
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Acetylcholine
Angiotensin II
Catecholamines
Dimethylphenylpiperazinium Iodide
Enalapril
Losartan
Veratridine
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