Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep

The Journal of Endocrinology
Christopher J CharlesA Mark Richards

Abstract

Emerging evidence suggests that the urocortin (UCN) peptides contribute to pressure and volume regulation with possible involvement in the pathophysiology of cardiovascular disease. We have recently reported that i.v. UCN1 potently inhibits cardiac sympathetic nerve activity (CSNA) in normal sheep. However, little is known about possible interactions between UCN2 and the sympathetic nervous system. Accordingly, we have examined the effects of i.v. UCN2 on CSNA, hemodynamics, and plasma catecholamines in normal conscious sheep. Bolus i.v. administration of UCN2 (25 and 100 mug) resulted in the expected hemodynamic actions including transient falls in arterial pressure (P=0.016) and more sustained rises in heart rate (P<0.001) and cardiac output (P<0.001) and falls in peripheral resistance (P<0.001). CSNA burst frequency showed a biphasic response (P<0.001) with an acute rise followed by a more prolonged fall. CSNA burst area and incidence showed prolonged, dose-dependent falls in response to UCN2 administration (all P<0.001). UCN2 also induced a short-lived rise in plasma norepinephrine levels (P=0.006). The marked rise in heart rate in response to UCN2 is preserved in sheep undergoing pharmacological ganglionic blockade with he...Continue Reading

Citations

May 2, 2012·International Journal of Endocrinology·Keiichi IkedaKatsuyoshi Tojo
Jun 8, 2012·International Journal of Endocrinology·Kazuhiro Takahashi
May 14, 2010·Future Cardiology·Jonathan R Dalzell, Colette E Jackson
Jul 16, 2015·Clinical and Experimental Pharmacology & Physiology·W Y Wandy ChanDavid L Jardine
Mar 10, 2015·Drug Discovery Today·Rui AdãoCarmen Brás-Silva
Jun 9, 2016·British Journal of Clinical Pharmacology·Colin G StirratDavid E Newby
Jun 12, 2013·Circulation. Heart Failure·Miriam T RademakerA Mark Richards
Jun 24, 2011·Journal of Cardiovascular Pharmacology·Christopher J CharlesA Mark Richards
May 9, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Christopher J CharlesA Mark Richards
Sep 13, 2019·Cardiovascular Drugs and Therapy·Cláudia Monteiro-PintoCarmen Brás-Silva
Dec 14, 2018·Expert Opinion on Investigational Drugs·Juan TamargoEva Delpón

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