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 mu g/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. (C) 1997 Academic Press Limited.