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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 (10-10 M) inhibited KCl (60 mM)-induced vasoconstriction in three types of small artery rings (pEC: 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 M)-induced vasoconstriction in mesenteric artery rings. The relaxant effect on the rat mesenteric artery was partially endothelium-dependent (pEC: 6.02 ± 0.05 for endothelium-intact and 5.72 ± 0.06 for endothelium-denuded). The influx and release of Ca 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, Ca channels, and the Rho/ROCK pathway. [ABSTRACT FROM AUTHOR]