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

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Background: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor withlosartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) fromthe 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 intoan 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-butynyltrimethylammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence ofenalapril 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 concentrationof 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. Inthe simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared withthat of enalapril- or losartan-treated alone. Conclusions: Collectively, these results demonstrate that both enalapril andlosartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in theperfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may alsobe of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seemsto be more potent than that of enalapril.

Abstract

Background: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor withlosartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) fromthe 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 intoan 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-butynyltrimethylammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence ofenalapril 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 concentrationof 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. Inthe simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared withthat of enalapril- or losartan-treated alone. Conclusions: Collectively, these results demonstrate that both enalapril andlosartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in theperfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may alsobe of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seemsto be more potent than that of enalapril.

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