Research on the Effects of the Chronic Treatment With Different Doses of Urocortin 2 in Heart Failure Rats

Corticotropin-releasing factor (CRF) receptor type 2 (CRF₂) exists in both cardiomyocytes and neurocytes. The purpose of this research was to explore if chronic treatment with urocortin 2 (UCN2), a CRF₂ receptor agonist, at different doses can improve prognosis and regulate the expression of CRF₂ receptor and calcium handling proteins without any adverse effects on behavior in heart failure. Heart failure was established in Sprague-Dawley rats and was confirmed by echocardiography. Heart failure rats were injected intraperitoneally with UCN2 (5, 10, or 20 µg·kg^-1·d^-1) for 30 days. Survival rate, cardiac function, expressions of cardiac CRF₂ receptor, RyR2, SERCA2, and hypothalamic and hippocampal c-FOS, CRF receptor type 1 (CRF₁) and CRF₂ receptor were determined. Behavior was evaluated by Morris Water-Maze and Open-Field tests. Results showed that chronic peripheral UCN2 treatment improved survival rate in a dose-response manner and increased cardiac function and expression of CRF₂ receptor and SERCA2 in heart failure, especially at the high dosage. Moreover, cellular-fos (c-FOS), CRF₁ receptor, and CRF₂ receptor expressions of both hypothalamic and hippocampal tissues were significantly increased in high dosage group. Furthermore, the behavior tests suggested that chronic UCN2 treatment did not exacerbate stress/anxiety-like behavior in HF. In conclusion, chronic peripheral treatment with UCN2 increases survival in a dose-response manner in heart failure rats without inducing stress/anxiety-like behavior.