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Mechanisms of Rho kinase regulation of vascular reactivity following hemorrhagic shock in rats.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2008 Jan; Vol. 29 (1), pp. 65-70. - Publication Year :
- 2008
-
Abstract
- Our previous research showed that Rho kinase took part in the regulation of vascular hyporeactivity after shock. The objective of the present study was to investigate its mechanism. With isolated superior mesenteric artery (SMA) from hemorrhagic shock rats, we studied the relationship of Rho kinase regulating vascular reactivity to calcium sensitivity and myosin light chain phosphatase (MLCP) and myosin light chain kinase (MLCK). The vascular reactivity and calcium sensitivity of SMA were observed by measuring the contraction initiated by accumulative norepinephrine (NE) and calcium under depolarizing condition (120 mM K(+)) with an isolated organ perfusion system. Hypoxia-treated vascular smooth muscle cells (VSMCs) were used to study the effects of Rho kinase on the activity of MLCP and MLCK and the phosphorylation of 20-kDa myosin light chain (MLC(20)). Myosin light chain (20 kDa) phosphorylation of VSMC in mesenteric artery was detected by immunoprecipitation and Western blotting. The activity of MLCP and MLCK was assayed by enzymatic catalysis. The contractile response of VSMC was measured by the ratio of accumulative infiltration of fluorescent isothiocyanate-conjugated bovine serum albumin through transwell. The results indicated that the vascular reactivity and calcium sensitivity of SMA to NE and calcium following hemorrhagic shock and the contractile response of VSMC to NE following hypoxia were significantly decreased. Angiotensin II (Ang-II), the Rho kinase stimulator, significantly improved hypoxia or hemorrhagic shock-induced decrease of vascular reactivity and calcium sensitivity. These effects of Ang-II on vascular reactivity were abolished by Y-27632, the specific Rho kinase inhibitor. Calyculin A, the MLCP inhibitor, further enhanced Ang-II-induced increase of calcium sensitivity, but ML-9, the MLCK inhibitor, had no effect. Further studies showed Ang-II reversed the hypoxia-induced increase of MLCP activity and increased the hypoxia-induced decrease of MLC(20) phosphorylation in VSMC. It was suggested that Rho kinase played an important role in the regulation of vascular reactivity after hemorrhagic shock. The mechanisms may be related to its calcium sensitivity regulation. Rho kinase up-regulates calcium sensitivity of VSMC possibly through inhibiting the activity of MLCP and increasing the phosphorylation of MLC(20).
- Subjects :
- Angiotensin II pharmacology
Animals
Azepines pharmacology
Calcium pharmacology
Cell Hypoxia physiology
In Vitro Techniques
Marine Toxins
Mesenteric Artery, Superior drug effects
Mesenteric Artery, Superior physiopathology
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle physiology
Myosin-Light-Chain Kinase antagonists & inhibitors
Myosin-Light-Chain Kinase physiology
Myosin-Light-Chain Phosphatase antagonists & inhibitors
Myosin-Light-Chain Phosphatase physiology
Oxazoles pharmacology
Rats
Rats, Wistar
rho-Associated Kinases antagonists & inhibitors
Shock, Hemorrhagic physiopathology
Vasoconstriction physiology
rho-Associated Kinases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1073-2322
- Volume :
- 29
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 17666953
- Full Text :
- https://doi.org/10.1097/shk.0b013e318063e477