Nicardipine Inhibits the Endothelin-1-Induced Constriction of Systemic Capacitance and Resistance Vessels

Abstract

We estimated the effects of intravenous injection of endothelin-1 (ET-1; 400 pmol/kg) on the systemic capacitance and resistance vessels in anesthetized mongrel dogs by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR), respectively. In addition, the present study investigated the inhibiting action of nicardipine (NIC; 10 micrograms/kg bolus injection followed by 1.0-2.0 micrograms/kg/min continuous infusion) against the vasoconstrictor action of ET-1. We examined the effects of ET-1 (30 to 1,000 pmol/0.1 ml) on the femoral arterial system by measuring the percent changes in the perfusion pressure (% delta PP) of the femoral artery perfused with a constant flow, and investigated the effect of NIC on the vasoconstrictor action of ET-1 in this preparation. We obtained the following results: (a) Intravenous injection of ET-1 raised both TPR and MCP. However, in the presence of NIC, ET-1 raised TPR without influencing MCP. (b) Intra-arterial injection of ET-1 caused a dose-dependent increase in % delta PP. NIC shifted the dose-response curve of ET-1 for % delta PP to the right in a parallel fashion.