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Cardiovascular Drugs and Therapy

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01-10-2014 | ORIGINAL ARTICLE

Vasodilatory Effect of a Novel Rho-Kinase Inhibitor, DL0805-2, on the rat Mesenteric Artery and its Potential Mechanisms

Authors: Tian-Yi Yuan, Yu Yan, Yu-Jie Wu, Xiao-Na Xu, Li Li, Xiao-Zhen Jiao, Ping Xie, Lian-Hua Fang, Guan-Hua Du

Published in: Cardiovascular Drugs and Therapy | Issue 5/2014

Abstract

Purpose

In the present study, we investigated the vasodilatory effect of a novel scaffold Rho-kinase inhibitor, DL0805-2, on isolated rat arterial rings including mesenteric, ventral tail, and renal arteries. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings.

Methods

A DMT multiwire myograph system was used to test the tension of isolated small arteries. Several drugs were employed to verify the underlying mechanisms.

Results

DL0805-2 (10⁻⁷–10⁻⁴ M) inhibited KCl (60 mM)-induced vasoconstriction in three types of small artery rings (pEC₅₀: 5.84 ± 0.03, 5.39 ± 0.03, and 5.67 ± 0.02 for mesenteric, renal, and ventral tail artery rings, respectively). Pre-incubation with DL0805-2 (1, 3, or 10 μM) attenuated KCl (10–60 mM) and angiotensin II (AngII; 10⁻⁶ M)-induced vasoconstriction in mesenteric artery rings. The relaxant effect on the rat mesenteric artery was partially endothelium-dependent (pEC₅₀: 6.02 ± 0.05 for endothelium-intact and 5.72 ± 0.06 for endothelium-denuded). The influx and release of Ca²⁺ were inhibited by DL0805-2. In addition, the increased phosphorylation levels of myosin light chain (MLC) and myosin-binding subunit of myosin phosphatase (MYPT1) induced by AngII were blocked by DL0805-2. However, DL0805-2 had little effect on K⁺ channels.

Conclusions

The present results demonstrate that DL0805-2 has a vasorelaxant effect on isolated rat small arteries and may exert its action through the endothelium, Ca²⁺ channels, and the Rho/ROCK pathway.

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Title: Vasodilatory Effect of a Novel Rho-Kinase Inhibitor, DL0805-2, on the rat Mesenteric Artery and its Potential Mechanisms
Authors: Tian-Yi Yuan
Yu Yan
Yu-Jie Wu
Xiao-Na Xu
Li Li
Xiao-Zhen Jiao
Ping Xie
Lian-Hua Fang
Guan-Hua Du
Publication date: 01-10-2014
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 5/2014
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-014-6544-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Vasodilatory Effect of a Novel Rho-Kinase Inhibitor, DL0805-2, on the rat Mesenteric Artery and its Potential Mechanisms

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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