title: Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia.
abstract: BACKGROUND
  The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia.
  
  
  METHODS
  Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats), and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP) and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP). Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM). The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting.
  
  
  RESULTS
  Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR) in response to PE-induced hypertension (+ΔMABP) (P < 0.05). In the presence of SNP, DMC increased the ΔMABP (P < 0.05). In addition, DMC markedly shortened the duration of blood pressure changes elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05). Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of neuropathology were largely prevented by treatment with DMC for 30 days. Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM rats, but had no effect on GABAA receptor expression.
  
  
  CONCLUSIONS
  The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.
authors.affiliation: Department of Pharmacology, and State-Province Key Laboratory of Biomedicine and Pharmaceutics, Harbin Medical University, Harbin 150081, PR China. a.z.hrbmu@gmail.com
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Guo-Fen
authors.initials: GF
authors.lastname: Qiao
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Sun
authors.forename: Guan-Yi
authors.initials: GY
authors.lastname: Lu
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002366:Cassia; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D005894:Panax; D010656:Phenylephrine / Q000494:pharmacology; D008517:Phytotherapy; D011311:Pressoreceptors / Q000187:drug effects* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012250:Rheum; D027561:Salvia miltiorrhiza
chemical_list: D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D009599:Nitroprusside; D010656:Phenylephrine; C104722:glutamate receptor ionotropic, AMPA 2