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Beneficial effects of platelet-derived growth factor on hemorrhagic shock in rats and the underlying mechanisms.

Abstract
Studies have shown that local application of platelet-derived growth factor (PDGF) can be used for the treatment of acute and chronic wounds. We investigated if systemic application of PDGF has a protective effect on acute hemorrhagic shock in rats in the present study. Using hemorrhagic shock rats and isolated superior mesenteric arteries, the effects of PDGF-BB on hemodynamics, animal survival, and vascular reactivity as well as the roles of the gap junction proteins connexin (Cx)40 and Cx43, PKC, and Rho kinase were observed. PDGF-BB (1–15 μg/kg iv) significantly improved the hemodynamics and blood perfusion to vital organs (liver and kidney) as well as vascular reactivity and improved the animal survival in hemorrhagic shock rats. PDGF recovering shock-induced vascular hyporeactivity depended on the integrity of the endothelium and myoendothelial gap junction. Cx43 antisense oligodeoxynucleotide abolished these improving effects of PDGF, whereas Cx40 oligodeoxynucleotide did not. Further study indicated that PDGF increased the activity of Rho kinase and PKC as well as vascular Ca2+ sensitivity, whereas it did not interfere with the intracellular Ca2+ concentration in hypoxia-treated vascular smooth muscle cells. In conclusion, systemic application of PDGF-BB may exert beneficial effects on hemorrhagic shock, which are closely related to the improvement of vascular reactivity and hemodynamics. The improvement of PDGF-BB in vascular reactivity is vascular endothelium and myoendothelial gap junction dependent. Cx43, Rho kinase, and PKC play very important role in this process. These findings suggest that PDGF may be a potential measure to treat acute clinical critical diseases such as severe trauma, shock, and sepsis.
AuthorsLiangming Liu, Jie Zhang, Yu Zhu, Xudong Xiao, Xiaoyong Peng, Guangming Yang, Jiatao Zang, Shangqing Liu, Tao Li
JournalAmerican journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 307 Issue 9 Pg. H1277-87 (Nov 01 2014) ISSN: 1522-1539 [Electronic] United States
PMID25172895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inducing Agents
  • Connexin 43
  • Connexins
  • Proto-Oncogene Proteins c-sis
  • connexin 40
  • Becaplermin
  • rho-Associated Kinases
  • Protein Kinase C
Topics
  • Angiogenesis Inducing Agents (pharmacology, therapeutic use)
  • Animals
  • Becaplermin
  • Calcium Signaling
  • Connexin 43 (genetics, metabolism)
  • Connexins (genetics, metabolism)
  • Endothelium, Vascular (drug effects, metabolism)
  • Gap Junctions (drug effects, metabolism, physiology)
  • Hemodynamics (drug effects)
  • Liver Circulation
  • Mesenteric Artery, Superior (cytology, metabolism, physiopathology)
  • Myocytes, Smooth Muscle (drug effects, metabolism)
  • Protein Kinase C (metabolism)
  • Proto-Oncogene Proteins c-sis (pharmacology, therapeutic use)
  • Rats
  • Rats, Wistar
  • Renal Circulation
  • Shock, Hemorrhagic (drug therapy, metabolism, physiopathology)
  • rho-Associated Kinases (metabolism)

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