Angiotensin II-Induced Vasoconstriction via Rho Kinase Activation in Pressure-Overloaded Rat Thoracic Aortas

Figures

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  Figure 1. Effects of various inhibitors on angiotensin II (Ang II)-induced contraction in sham-operated (Sham) or pressure-overloaded (Banding) rat thoracic aortic rings. (A): Y-27632 (Y: 10 µmol/L); (B): AG1478 (AG: 10 µmol/L); (C): PP2 (3 µmol/L); (D): TAPI-0 (TAPI: 10 µmol/L); (E): FR180204 (FR: 10 µmol/L); and (F): JAK2 inhibitor II (JAK: 10 µmol/L) was added 15 min before Ang II treatment. The Magnus measure we used in the experiment consists of eight chambers. The thoracic aorta was removed from the rat, cut into about 10 segments, and each segment was attached to the chamber. Chamber A is for control (cumulative addition of Ang II), and chambers B to F are pretreated with an inhibitor, and then Ang II is cumulatively added. The figure was created based on the contraction data obtained from each chamber. Cumulative contraction response curves normalized to 40 mmol/L KCl-induced contraction. Data are means ± S.E.M. for thoracic aortic rings from 4−12 rats, * p < 0.05 vs. Sham, † p < 0.05 vs. Banding.

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  Figure 2. Expression of total and phosphorylated Src (A), Erk1/2 (B), MYPT1 (C), and JAK2 (D) in thoracic aortas from sham-operated (Sham) or pressure-overloaded (Banding) rats. Upper: representative blots. Lower: scatter plots demonstrating densitometric quantification of the ratios of total or phosphorylated proteins to the corresponding β-actin or total proteins, respectively. Results are shown as the fold increase relative to Sham. Data are means ± S.E.M. of four independent experiments, * p < 0.05 vs. Sham.

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  Figure 3. Proposed mechanisms underlying angiotensin II (Ang II)-induced aortic contraction in normotensive or pressure-overloaded condition. In normotensive condition, Ang II induces aortic contraction via epidermal growth factor receptor (EGFR), Src, metalloproteinase, extracellular signal-regulated kinase 1 and 2 (Erk1/2), and Rho kinase. In pressure-overloaded condition, Ang II induces aortic contraction via EGFR, Erk1/2, Rho kinase, and Janus kinase 2 (JAK2). Moreover, Ang II-induced aortic contraction is augmented in pressure-overloaded condition probably because the protein expression of JAK2 and myosin phosphatase targeting subunit 1 is increased. AT1R, Ang II type 1 receptor.