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(Circulation Research. 2003;93:1015.)
© 2003 American Heart Association, Inc.

Editorials

Cellular Mechanism of Vasoconstriction Induced by Angiotensin II

It Remains To Be Determined

Hideo Kanaide, Toshihiro Ichiki, Junji Nishimura, Katsuya Hirano

From the Division of Molecular Cardiology (H.K., J.N., K.H.) and Cardiovascular Medicine (T.I.), Research Institute of Angiocardiology, Graduate School of Medical Sciences, and Kyushu University COE Program on Lifestyle-Related Diseases, Kyushu University, Fukuoka, Japan.

Correspondence to Hideo Kanaide, MD, PhD, Professor, Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, Japan 812-8582. E-mail kanaide@molcar.med.kyushu-u.ac.jp

Key Words: angiotensin II • AT1 subtype • calcium signaling • vasoconstriction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Circulation Research, using mouse large conduit arteries, Zhou et al¹ have provided direct evidence that AT1b, a subtype of angiotensin (Ang) II type 1 (AT1) receptors, predominantly mediates contractions induced by Ang II. In Figure 3, when 100 nmol/L Ang II was applied to the abdominal aorta and the femoral artery of knockout mice for AT1a, biphasic responses in tension appeared. Tension rose rapidly and transiently peaked in a few minutes, and then declined to a lower steady level (close to the preapplication level) at 10 to 20 minutes. Thus, Ang II causes a rapid contraction that attenuates significantly after several minutes even in the continued presence of agonist. However, the mechanisms underlying the biphasic response to Ang II are not explained in the report.

Stimulation of AT1 receptors leads to activation, via the G protein Gq, of phospholipase C, which hydrolyzes phosphatidylinositol-4,5-bisphosphate to generate inositol-1,4,5-trisphosphate (IP₃) and diacylglycerol (DG). IP₃ triggers the intracellular release of Ca²⁺, and additional Ca²⁺ enters the cell from outside due to opening of Ca²⁺ channels located in the cell membrane. Ca²⁺/calmodulin-dependent myosin light chain kinase (MLCK) can switch on MLC phosphorylation and tension development. The extent of MLC phosphorylation reflects the activities of both MLCK and MLC phosphatase (MLCP). Thus, at constant Ca²⁺ and MLCK activity, inhibition of MLCP will cause an increase in MLC phosphorylation and tension, a phenomenon called Ca²⁺ sensitization. There are two well-described myosin phosphatase inhibitory pathways.² The first is the RhoA/Rho-kinase . . . [Full Text of this Article]

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