title: Baroreflex deficiency hampers angiogenesis after myocardial infarction via acetylcholine-α7-nicotinic ACh receptor in rats.
abstract: OBJECTIVE
  Angiogenesis is critical for re-establishing blood supply to ischaemic myocardium after myocardial infarction (MI). Human studies have associated arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI. The present work was designed to examine whether ABR deficiency affects angiogenesis in MI rats.
  
  
  RESULTS
  Baroreflex sensitivity (BRS) was determined in conscious rats at 1 month after occlusion of the left anterior descending coronary artery. The survival time was significantly shorter in Sprague-Dawley rats with BRS <0.60 ms/mmHg vs. those with BRS ≥0.60 ms/mmHg. Sinoaortic denervation destroyed ABR, and decreased capillary density, regional blood flow and vascular endothelial growth factor (VEGF) concentration after MI. Ketanserin (0.6 mg/kg/day) enhanced BRS, and increased capillary density, regional blood flow, and VEGF. Sinoaortic denervation also reduced the expression of vesicular acetylcholine (ACh) transporter and α7-nicotinic ACh receptor (α7-nAChR). Angiogenesis after MI was significantly attenuated in α7-nAChR knockout mice. In contrast, increase in endogenous ACh with cholinesterase inhibitor pyridostigmine (30 mg/kg/day) increased angiogenesis after MI. In cultured cardiac microvascular endothelial cells, ACh stimulated the expression of VEGF, phosphorylation of VEGF receptor 2, and tube formation in a manner dependent upon α7-nAChR.
  
  
  CONCLUSIONS
  Our results demonstrated that ABR deficiency could attenuate angiogenesis in ischaemic myocardium. These findings provide further mechanistic basis for enhancing baroreflex function in the treatment of MI.
authors.affiliation: Department of Pharmacology, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors.forename: Jian-Guang
authors.initials: JG
authors.lastname: Yu
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Song
authors.forename: He
authors.initials: H
authors.lastname: Shu
authors.forename: Sai-Jun
authors.initials: SJ
authors.lastname: Fan
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Liu
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Jin-Min
authors.initials: JM
authors.lastname: Guo
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Miao
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D003714:Denervation / Q000379:methods; D007650:Ketanserin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D018679:Cholinergic Agonists; D002800:Cholinesterase Inhibitors; D064569:alpha7 Nicotinic Acetylcholine Receptor; D007650:Ketanserin; D011729:Pyridostigmine Bromide; D000109:Acetylcholine