Mechanism of Human Urotensin II-Induced Contraction in Rat Aorta

• Main Authors: Katsunari Tasaki, Masatoshi Hori, Hiroshi Ozaki, Hideaki Karaki, Ichiro Wakabayashi
• Format: Article
• Language: English
• Published: Elsevier 2004-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319324727

Urotensin II induced sustained contraction with an EC50 value of 2.29 ± 0.12 nM in rat aorta. Urotensin II (100 nM) transiently increased cytosolic Ca2+ level ([Ca2+]i), followed by a small sustained phase superimposed with rhythmic oscillatory change. In the presence of verapamil and La3+, the [Ca2+]i oscillation was completely inhibited, although a small transient increase in [Ca2+]i remained. The urotensin II-induced contraction was also partially inhibited by verapamil and La3+. Combined application of verapamil, La3+, and thapsigargin completely inhibited the increase in [Ca2+]i with only partial inhibition of the contraction elicited by urotensin II. Urotensin II increased myosin light chain (MLC) phosphorylation to a level greater than that induced by 72.7 mM KCl (high K+). Pretreatment with Go6983 (PKC inhibitor), U0126 (MEK inhibitor), or SB203580 (p38MARK inhibitor) partially inhibited the urotensin II-induced contraction with no effects on the high K+-induced contractions. Wortmannin (MLC kinase inhibitor) only partially inhibited urotensin II-induced contraction, although it completely inhibited the high K+-induced contraction. These results suggest that urotensin II-induced contraction is mediated by the Ca2+/calmodulin/MLC kinase system and modulated by the Ca2+ sensitization mechanisms to increase MLC phosphorylation. In addition, activations of PKC, p38MAPK, and ERK1/2 modulate the contractility mediated by urotensin II in rat aorta. Keywords:: urotensin II, rat aorta, Ca2+, myosin phosphorylation, Ca2+ sensitization