Resveratrol is an arginase inhibitor contributing to vascular smooth muscle cell vasoconstriction via increasing cytosolic calcium

Choi,Chang  Ik; Koo,Bon  Hyeock; Hong,Dongeui; Kwon,Hyung  Joo; Hoe,Kwang  Lae; Won,Moo  Ho; Kim,Young  Myeong; Lim,Hyun  Kyo; Ryoo,Sungwoo

doi:10.3892/mmr.2019.10035

Resveratrol is an arginase inhibitor contributing to vascular smooth muscle cell vasoconstriction via increasing cytosolic calcium

Authors:
- Chang Ik Choi
- Bon Hyeock Koo
- Dongeui Hong
- Hyung Joo Kwon
- Kwang Lae Hoe
- Moo Ho Won
- Young Myeong Kim
- Hyun Kyo Lim
- Sungwoo Ryoo
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Affiliations: Department of Anesthesiology and Pain Medicine, Yonsei University Wonju College of Medicine, Wonju, Gangwon 26426, Republic of Korea, Department of Biology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Microbiology, School of Medicine, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of Korea, Department of Neurobiology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Molecular and Cellular Biochemistry, and Neurobiology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
Published online on: March 14, 2019 https://doi.org/10.3892/mmr.2019.10035
Pages: 3767-3774

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Abstract

The contractility of vascular smooth muscle cells (VSMCs) controls the lumen diameter of vessels, thus serving a role in regulating blood pressure and organ blood flow. Although arginases are known to have numerous effects in the biological activities of VSMCs, the effects of arginase II on the constriction of VSMCs has not yet been investigated. When conducting a natural products screen for an inhibitor against arginase, the present study identified that a relatively high concentration of resveratrol (RSV) exhibited arginase inhibitory activity. Therefore, the present study investigated whether RSV could regulate VSMCs contractions and the underlying mechanism. Arginase inhibition by RSV led to an increase in the concentration of the substrate L‑Arg and an accompanying increase in the cytosol Ca2+ concentration [(Ca2+)c] in VSMCs. The increased [Ca2+]c induced by RSV and L‑Arg treatments resulted in CaMKII‑dependent MLC20 phosphorylation. The effects of RSV on VSMCs were maintained even when VSMCs were pre‑treated with sirtinol, an inhibitor of Sirt proteins. In a vascular tension assay with de‑endothelialized aortic vessels, vasoconstrictor responses, which were measured using phenylephrine (PE), were significantly enhanced in the RSV‑ and L‑Arg‑treated vessels. Therefore, although arginase inhibition has exhibited beneficial effects in various diseases, care is required when considering administration of an arginase inhibitor to patients with vessels endothelial dysfunction as RSV can induce vessel contraction.

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