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


CONCLUSIONS
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.
Charles
Christopher J
CJ
Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand. chris.charles@chmeds.ac.nz
Jardine
David L
DL
Nicholls
M Gary
MG
Rademaker
Miriam T
MT
Richards
A Mark
AM
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D009433:Neural Inhibition / Q000187:drug effects*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D054832:Urocortins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014851:Wakefulness
D002395:Catecholamines; D054832:Urocortins