Document Detail

Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep.
MedLine Citation:
PMID:  19914944     Owner:  NLM     Status:  MEDLINE    
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 hexamethonium. In conclusion, this is the first study to report the effects of UCN2 on SNA and indicates potent inhibition of sympathetic traffic to the heart despite a generalized baroreceptor-induced activation of sympathetic activity. These findings suggest an important role for UCN2 in cardiovascular homeostasis and warrant further investigation for potential therapeutic applications in acute myocardial injury and heart disease.
Christopher J Charles; David L Jardine; Miriam T Rademaker; A Mark Richards
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-13
Journal Detail:
Title:  The Journal of endocrinology     Volume:  204     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-19     Completed Date:  2010-03-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  181-9     Citation Subset:  IM    
Christchurch Cardioendocrine Research Group, University of Otago, Christchurch, Christchurch 8140, New Zealand.
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MeSH Terms
Catecholamines / blood*
Ganglionic Blockers
Sympathetic Nervous System / physiology*
Urocortins / physiology*
Reg. No./Substance:
0/Catecholamines; 0/Ganglionic Blockers; 0/Urocortins; 60-26-4/Hexamethonium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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