title: Detrimental Impact of Vasopressin V2 Receptor Antagonism in a SU5416/Hypoxia/Normoxia-Exposed Rat Model of Pulmonary Arterial Hypertension.
abstract: BACKGROUND
  The expression of vasopressin type 2 receptor (V2R) in the lung, and the long-term effects of tolvaptan, a selective V2R antagonist, on pulmonary circulation and right ventricular (RV) remodeling in a pulmonary arterial hypertension (PAH) rat model were evaluated.
  
  
  RESULTS
  Six-week-old male Sprague-Dawley rats were injected subcutaneously with 20 mg/kg of SU5416 and were exposed to hypoxia for 3 weeks followed by re-exposure to normoxia for 7 weeks. These rats showed signs of RV failure and upregulation of V2R and cAMP in the lung tissue at 10 weeks after SU5416 injection. They were then treated with either 0.05% tolvaptan in diet (SUHx+Tolv) or normal diet (SUHx) during 5-10 weeks of SU5416 injection. Normal control rats (Cont) were also used for comparison. SUHx+Tolv had significantly higher pulmonary arterial pressure, more progressive pulmonary arterial remodeling, and more severe myocyte hypertrophy and interstitial myocardial fibrosis in the right ventricle compared with SUHx despite achieving successful preload reduction.
  
  
  CONCLUSIONS
  Chronic vasopressin V2R antagonism may contribute to the worsening of PAH and the development of RV remodeling.
authors.affiliation: Department of Cardiology and Nephrology, Mie University Graduate School of Medicine.
authors.forename: Itaru
authors.initials: I
authors.lastname: Goto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Dohi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ogihara
authors.forename: Ryuji
authors.initials: R
authors.lastname: Okamoto
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yamada
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mitani
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D011758:Pyrroles / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D011758:Pyrroles; D017483:Receptors, Vasopressin; C116890:Semaxinib