Effects of cardiotrophin-1 on haemodynamics and cardiac function in conscious rats.
Cardiotrophin-1 (CT-1), a newly discovered cytokine, has been shown to induce cardiac hypertrophy in vitro and in vivo. The present study examined the effects of CT-1 on haemodynamics and cardiac function. The measurements of haemodynamic parameters were made using in-dwelling catheters and flow probes in conscious, unrestrained rats. Intravenous administration of CT-1 caused a dose-dependent decrease in mean arterial pressure (MAP), and an increase in heart rate (HR). CT-1 (100 micrograms/kg) significantly elevated cardiac output and HR, and decreased MAP and systemic vascular resistance. Stroke volume was unaltered, suggesting that the CT-1 induced increase in cardiac output was secondary to increased HR. There was no significant difference in left ventricular maximal dP/dt between the CT-1-treated and vehicle-treated groups, suggesting that CT-1 might not induce a meaningful change in ventricular contractility. Pretreatment with intravenous N omega-nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide synthase, significantly attenuated the depressor and tachycardic responses to CT-1. These results indicate that nitric oxide plays an important role in mediating the haemodynamic effects of CT-1.
Jin
H
H
Department of Cardiovascular Research, Genentech Inc., South San Francisco, CA 94080, USA. hkj@gene.com
Yang
R
R
Ko
A
A
Pennica
D
D
Wood
W I
WI
Paoni
N F
NF
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013610:Tachycardia; D016277:Ventricular Function, Left / Q000187:drug effects
D016207:Cytokines; D009569:Nitric Oxide; C092073:cardiotrophin 1