title: Raisanberine protected pulmonary arterial rings and cardiac myocytes of rats against hypoxia injury by suppressing NADPH oxidase and calcium influx.
abstract: OBJECTIVE
  To investigate the protection of pulmonary arterial rings and cardiac myocytes of rats by raisanberine (RS), a derivative of berberine, against hypoxia injury and to elucidate the action mechanisms.
  
  
  METHODS
  Adult SD rats were exposed to intermittent hypoxia for 17 d or 28 d. The pulmonary arterial rings were isolated and vascular activity was measured using a transducer and computer-aided system. The difference in the tension produced by phenylephrine in the presence and absence of L-nitroarginine (10 μmol/L) was referred to as the NO bioavailability; the maximum release of NO was assessed by the ratio of the maximal dilatation caused by ACh to those caused by sodium nitroprusside. After the lungs were fixed, the internal and the external diameters of the pulmonary arterioles were measured using a graphic analysis system. Cultured cardiac myocytes from neonatal rats were exposed to H(2)O(2) (10 μmol/L) to mimic hypoxia injury. ROS generation and [Ca(2+)](i) level in the myocytes were measured using DHE and Fluo-3 fluorescence, respectively.
  
  
  RESULTS
  Oral administration of RS (80 mg/kg), the NADPH oxidase inhibitor apocynin (APO, 80 mg/kg) or Ca(2+) channel blocker nifedipine (Nif, 10 mg/kg,) significantly alleviated the abnormal increase in the vasoconstriction force and endothelium-related vasodilatation induced by the intermittent hypoxia. The intermittent hypoxia markedly decreased the NO bioavailability and maximal NO release from pulmonary arterial rings, which were reversed by APO or RS administration. However, RS administration did not affect the NO bioavailability and maximal NO release from pulmonary arterial rings of normal rats. RS, Nif or APO administration significantly attenuated the pulmonary arteriole remodeling. Treatment of cultured cardiac myocytes with RS (10 μmol/L) suppressed the ROS generation and [Ca(2+)](i) increase induced by H(2)O(2), which were comparable to those caused by APO (10 μmol/L) or Nif (0.1 μmol/L).
  
  
  CONCLUSIONS
  Raisanberine relieved hypoxic/oxidant insults to the pulmonary artery and cardiac myocytes of rats by suppressing activated NADPH oxidase and increased calcium influx.
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Yi-qun
authors.initials: YQ
authors.lastname: Tang
authors.forename: De-zai
authors.initials: DZ
authors.lastname: Dai
authors.forename: Yu-si
authors.initials: YS
authors.lastname: Cheng
authors.forename: Guo-lin
authors.initials: GL
authors.lastname: Zhang
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology; D001599:Berberine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C400084:4-chlorobenzyltetrahydroberberine; D000975:Antioxidants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001599:Berberine; D009569:Nitric Oxide; D019255:NADPH Oxidases