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Simvastatin reduces adrenal catecholamine secretion evoked by stimulation of cholinergic nicotinic and angiotensinergic AT1 receptors

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Abstract

We investigated the influence of simvastatin, a statin, on the secretion of catecholamines (CA) in rat adrenal glands, and clarified its action mechanism. Simvastatin suppressed acetylcholine (ACh)-evoked CA release in a dose- and time-dependent fashion. In the presence of simvastatin, CA secretion evoked by 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), angiotensin II, high K+, veratridine, and Bay-K-8644 was time-dependently inhibited. However, in the simultaneous presence of simvastatin and Nω-nitro-l-arginine methyl ester hydrochloride, CA secretion evoked by angiotensin II and DMPP recovered to control levels. Adrenal NO release was increased by simvastatin-treatment. Simvastatin-inhibited CA secretion was not affected by treatment with mevalonate. Pravastatin did not influence ACh-evoked CA secretion, while atorvastatin reduced it. In the simultaneous presence of simvastatin and fimasartan, ACh-induced CA release was markedly reduced compared to that of fimasartan-treatment alone. We present the first evidence that simvastatin reduces adrenal CA secretion induced by stimulation of nicotinic and AT1-receptors. Simvastatin-induced inhibition seems to involve reducing the influx of both Ca2+ and Na+ into adrenochromaffin cells, partly via the elevation of NO production by NO synthase activation, without inhibition of 3-hydroxy-methylglutaryl coenzyme A reductase. Co-administration of simvastatin and fimasartan may be clinically helpful for the treatment of cardiovascular diseases.

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Acknowledgements

This study was supported by the research fund provided from Chosun University (2015–2016).

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Authors and Affiliations

  1. Department of Pediatrics, College of Medicine, Chosun University, Kwangju, 61453, Korea

    Young-Kwon Koh

  2. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, 07061, Korea

    Ki-Hwan Kim

  3. Department of Leisure & Sport, College of Public Health and Welfare, Dongshin University, Naju, Chollanam-Do Province, 58245, Korea

    Mee-Sung Choi

  4. Department of Internal Medicine (Cardiology), College of Medicine, Chosun University, Gwangju, 501-759, Korea

    Young-Youp Koh

  5. Department of Pharmacology, College of Medicine, Chosun University, 309 Pilmoondae-Ro, Dong-Gu, Gwangju, 61452, Korea

    Dong-Yoon Lim

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  1. Young-Kwon Koh
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Koh, YK., Kim, KH., Choi, MS. et al. Simvastatin reduces adrenal catecholamine secretion evoked by stimulation of cholinergic nicotinic and angiotensinergic AT1 receptors. Arch. Pharm. Res. 41, 333–346 (2018). https://doi.org/10.1007/s12272-018-1007-5

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