title: Involvement of Rho-kinase in collar-induced vasoconstriction and vascular hypersensitivity to serotonin in rat carotid.
abstract: BACKGROUND
  Vasoconstriction and vascular hypersensitivity to serotonin has been described previously in animal models of adventitia injury. The present study was undertaken to investigate the contribution of the RhoA/Rho-kinase pathway to the collar-induced the change of vascular contractility and reactivity in rat carotid artery.
  
  
  METHODS
  Wistar Kyoto rats were assigned to 4 treatments (n=12): vehicle, fasudil, valsartan, and fasudil plus valsartan. After 1 week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for 1 week. Blood flow and vascular reactivity to serotonin was determined 1 week after injury, and carotids were harvested for morphometry and biochemical analysis.
  
  
  RESULTS
  Adventitia injury leaded to histological changes of vasoconstriction with the percent lumen patency of 54.5 ± 4.3% (p<0.001) decreasing, accompanying by the reduction of the blood flow (2.79 ± 0.22 ml/min vs. 3.67 ± 0.26 mi/min/p<0.001) when compared to contralateral arteries. The increase of vascular reactivity sensitivity to serotonin was observed in the collared artery when compared with the contralateral artery. Treatment with valsartan and fasudil prevented the development of vasoconstriction, improved the carotid blood flow and normalized the hypersensitivity to serotonin. Injury increased Angiotensin II type 1(AT(1)receptor, Rho-kinase, and p-MYPT1(Thr696) expression. Valsartan lowered the Rho-kinase and p-MYPT1(Thr696) expression. Fasudil inhibited the p-MYPT1(Thr696) expression.
  
  
  CONCLUSIONS
  Collar-induced adventitia injury resulted in the enhancement of vascular contractility and reactivity. The activation of RhoA/Rho-kinase signal pathway, stimulated by AT(1) receptor, plays an important role in the collar-induced the change of vascular contractility and reactivity.
authors: Cardiology Department, First Hospital of China Medical University, North 2nd Road No.92, Heping Ward, Shenyang 110001, China.
authors: Lianna
authors: L
authors: Xie
authors: Dingyin
authors: D
authors: Zeng
authors: Haishan
authors: H
authors: Zhang
authors: Danmeng
authors: D
authors: Sun
authors: Xuefeng
authors: X
authors: Pang
authors: Qigang
authors: Q
authors: Guan
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012828:Silicones; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D047428:Protein Kinase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D012828:Silicones; D013777:Tetrazoles; D012701:Serotonin; D000068756:Valsartan; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D014633:Valine; C049347:fasudil