Effect of MCI-154 on calcium sensitivity of vascular smooth muscle and its mechanism in hemorrhagic shock in rats
OBJECTIVE: To observe the effects of new calcium sensitizer MCI-154 on calcium sensitivity of vascular smooth muscle following hemorrhagic shock (HS) in rats, and to explore its mechanism
| Veröffentlicht in: | Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue. - 1998. - 17(2005), 1 vom: 06. Jan., Seite 7-11 |
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| Format: | Aufsatz |
| Sprache: | Chinese |
| Veröffentlicht: |
2005
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| Zugriff auf das übergeordnete Werk: | Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue |
| Schlagworte: | English Abstract Journal Article Research Support, Non-U.S. Gov't Pyridazines Vasodilator Agents MCI 154 98326-33-1 rho-Associated Kinases EC 2.7.11.1 Cyclic GMP-Dependent Protein Kinases mehr... |
| Zusammenfassung: | OBJECTIVE: To observe the effects of new calcium sensitizer MCI-154 on calcium sensitivity of vascular smooth muscle following hemorrhagic shock (HS) in rats, and to explore its mechanism METHODS: The superior mesenteric artery (SMA) from HS model of rat was adopted to assay the calcium sensitivity via observing the contraction initiated by Ca2+ under depolarizing conditions (120 mmol/L K+) with isolated organ perfusion system. The experiment was conducted in two parts, the effects of MCI-154 on calcium sensitivity of vascular smooth muscle in HS, and to explore whether MCI-154 could regulate the calcium sensitivity through regulating Rho-kinase, protein kinase C (PKC) and protein kinase G(PKG) RESULTS: Compared with the normal control group, the cumulative dose-response curve of SMA to Ca2+ in shock group was shifted to the right, the maximal contraction to Ca2+ was decreased significantly (P<0.01). MCI-154(10(-7), 10(-6), 10(-5), 10(-4) mol/L) pretreatment further shift the cumulative dose-response curve of Ca2+ to the right as compared to shock group (P<0.01). These result suggested that calcium desensitization existed in the vascular smooth muscle following HS, and MCI-154 further decreased the calcium sensitivity. Angiotensin II and phorbol 12-myristate-13-acetate (PMA), the Rho-kinase agonist and PKC agonist, increased the calcium sensitivity, made the cumulative dose-response curve of Ca2+ shift to the left. After MCI-154(10(-5) mol/L) pretreatment, the dose-response curve of Ca2+ was shifted to the right as compared to Ang II and PMA alone group (P<0.01). But, KT-5823, the PKG antagonist, antagonized MCI-154-induced right shift of the dose-response curve of Ca2+. It was suggested that MCI-154 induced the decrease of calcium sensitivity might be related to Rho-kinase, PKC and PKG CONCLUSION: The calcium sensitivity of vascular smooth muscle following HS is significantly decreased, MCI-154 can further decrease calcium sensitivity. MCI-154 may regulate calcium sensitivity of vascular smooth muscle through Rho-kinase, PKC and PKG |
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| Beschreibung: | Date Completed 08.10.2009 Date Revised 20.11.2014 published: Print Citation Status MEDLINE |
| ISSN: | 1003-0603 |