Urocortin 3 inhibits cardiac sympathetic nerve activity in conscious sheep

There is an increasing body of evidence suggesting a role for the urocortin (Ucn) peptides in blood pressure regulation and in the pathophysiology of cardiovascular disease. Both Ucn1 and Ucn2 have recently been shown to inhibit cardiac sympathetic nerve activity (CSNA) in sheep. However, there are few studies reporting the effects of Ucn3 on the sympathetic nervous system. Hence, this study performed in normal conscious sheep examines the effects of Ucn3 on CSNA. Intravenous Ucn3 (administered at doses of 25 and 100 μg) caused transient falls in arterial pressure (P = 0.025), more prolonged rises in heart rate (P < 0.001), and falls in stroke volume (P < 0.001) and peripheral resistance (P = 0.018). CSNA, measured as burst area and burst incidence, fell in a dose-dependent manner after Ucn3 bolus (all P < 0.001). CSNA burst frequency tended to be reduced after high-dose Ucn3. Ucn3 had no significant effect on plasma catecholamine levels. In conclusion, this study reports for the first time that Ucn3 induces potent inhibition of sympathetic traffic directed toward the heart. This provides further support for a role for Ucn3 in pressure and volume homeostasis and suggests that further investigation of potential therapeutic applications for Ucn3 in cardiovascular disease is warranted.