Detrimental Impact of Vasopressin V2 Receptor Antagonism in a SU5416/Hypoxia/Normoxia-Exposed Rat Model of Pulmonary Arterial Hypertension
| Autor: | Norikazu Yamada, Masaaki Ito, Yoshihide Mitani, Ryuji Okamoto, Kaoru Dohi, Itaru Goto, Yoshito Ogihara |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Receptors Vasopressin medicine.medical_specialty Vasopressin Indoles Normal diet Hypertension Pulmonary Tolvaptan 030204 cardiovascular system & hematology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Internal medicine Arginine vasopressin receptor 2 medicine Animals Pyrroles Hypoxia Ventricular remodeling Vasopressin receptor Ventricular Remodeling business.industry General Medicine Hypoxia (medical) medicine.disease Pulmonary hypertension Rats Up-Regulation Disease Models Animal 030104 developmental biology Endocrinology Cardiology medicine.symptom Cardiology and Cardiovascular Medicine business Antidiuretic Hormone Receptor Antagonists medicine.drug |
| Zdroj: | Circulation Journal. 80:989-997 |
| ISSN: | 1347-4820 1346-9843 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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