Urocortin 1 exhibits potent inhibition of cardiac sympathetic nerve activity in conscious sheep.

Abstract:

OBJECTIVES:Urocortin 1 (Ucn1) and the sympathetic nervous system both participate in cardiac and circulatory regulation, but little is known about their possible interactions. METHODS:We report the effects of Ucn1 on the cardiac sympathetic nerve activity (CSNA), haemodynamics and plasma catecholamines in normal sheep. RESULTS:Bolus intravenous administration of Ucn1 at 2.5 and 10 microg in seven sheep had no significant effect on haemodynamic parameters, including heart rate, mean arterial pressure (MAP) and cardiac output. At these doses, however, Ucn1 administration reduced CSNA, with burst frequency (P = 0.011), burst incidence (P = 0.015) and burst area (P = 0.012) all significantly reduced in a dose-related manner compared with a time-matched control. At higher doses (25 and 100 microg; n = 5 sheep), Ucn1 induced significant rises in heart rate (P < 0.001) and cardiac output (P = 0.03) and reduced peripheral resistance (P = 0.03), but had no effect on MAP. Ucn1 administration at the higher doses reduced CSNA, with burst incidence (P < 0.001), burst area/min (P = 0.001) and burst area/100 beats (P < 0.001) all significantly reduced in a dose-related manner compared with a time-matched control. There was no change in plasma catecholamines at any dose. CONCLUSION:The present study shows that Ucn1 induces potent inhibition of sympathetic traffic to the heart at doses both above and below the threshold for direct actions of Ucn1 on the myocardium. These findings suggest an important role for Ucn1 in cardiovascular homeostasis and warrant further investigation for potential therapeutic applications in acute myocardial injury and heart disease.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Charles CJ,Jardine DL,Nicholls MG,Rademaker MT,Richards AM

doi

10.1097/HJH.0b013e3282f01428

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

53-60

issue

1

eissn

0263-6352

issn

1473-5598

pii

00004872-200801000-00011

journal_volume

26

pub_type

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