Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Pulmonary Circulation
Detrimental Impact of Vasopressin V2 Receptor Antagonism in a SU5416/Hypoxia/Normoxia-Exposed Rat Model of Pulmonary Arterial Hypertension
Itaru GotoKaoru DohiYoshito OgiharaRyuji OkamotoNorikazu YamadaYoshihide MitaniMasaaki Ito
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Supplementary material

2016 Volume 80 Issue 4 Pages 989-997

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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.Methods and 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. (Circ J 2016; 80: 989–997)

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© 2016 THE JAPANESE CIRCULATION SOCIETY
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