title: The effects of vasoactive peptide urocortin 2 on hemodynamics in spontaneous hypertensive rat and the role of L-type calcium channel and CRFR2.
abstract: BACKGROUND
  Urocortin (UCN) is a newly identified vascular-active peptide that has been shown to reverse cardiovascular remodeling and improve left ventricular (LV) function. The effects and mechanism of urocortin 2 (UCN2) in vivo on the electrical remodeling of left ventricle and the hemodynamics of hypertensive objectives have not been investigated.
  
  
  METHODS
  UCN2 (1 μg/kg/d, 3.5 μg/kg/d or 7 μg/kg/d) was intravenously injected for 2 weeks and its effects on hemodynamics in spontaneously hypertensive rats (SHRs) observed. The whole-cell patch clamp technique was used to explore the effects of UCN2 on the electrical remodeling of left ventricular cardiomyocytes. The flow cytometry method was used to determine the content of fluorescence calcium in myocardium.
  
  
  RESULTS
  UCN2 improved the systolic and diastolic function of SHRs as demonstrated by decreased left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), increased +dp/dtmax and -dp/dtmax and decreased cAMP level. UCN2 inhibited the opening of L-type calcium channel and decreased the calcium channel current of cardiomyocytes. In addition, UCN2 also decreased the contents of fluorescence calcium in SHR myocardium. However, astressin2-B (AST-2B), the antagonist of corticotropin-releasing factor receptor 2 (CRFR2), could reverse the inhibitory effects of UCN2 on calcium channel.
  
  
  CONCLUSIONS
  UCN2 can modulate electrical remodeling of the myocardium and hemodynamics in an experimental model of SHR via inhibition of L-type calcium channel and CRFR2 in cardiomyocytes.
authors.affiliation: Department of Pharmacology, Liaoning Medical University, JinZhou, China. Electronic address: springnanaliu@163.com.
authors.forename: Chunna
authors.initials: C
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, JinZhou, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Liaoning Medical University, JinZhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, JinZhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Duan
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, JinZhou, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Yao
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, JinZhou, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Liaoning Medical University, JinZhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D054832:Urocortins / Q000494:pharmacology* / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: C101531:CRF receptor type 2; D020746:Calcium Channels, L-Type; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C528574:astressin-2B; C514216:urocortin 3, rat; D003346:Corticotropin-Releasing Hormone; D002118:Calcium
keywords: Corticotropin releasing factor; L-type calcium channel; Patch clamp; Spontaneously hypertension; Urocortin