Endothelin ET A receptor antagonism attenuates the pressor effects of nicotine in rats

Abstract

The increased endothelin-1 levels observed after smoking may result from nicotine-stimulated endothelin-1 production by endothelial cells. In this study, we investigated the effects of selective endothelin ET A receptors antagonist Cycle d- a-aspartyl- l-prolyl- d-isoleucyl- d-tryptophyl (JKC 301) and of endothelin ET B receptors antagonist N- cis-2,6-dimethylpiperidino-carbonyl- l-gamma-methyl-leucyl- d- l- m ethoxycarbonyl-tryptophanyl-norleucine (BQ 788) on the changes in mean arterial pressure, heart rate, and plasma thromboxane B 2 (the stable product of thromboxane A 2) levels caused by increasing doses of nicotine (0.6, 2, 6, and 20 μmol/kg) in anesthetised rats. Nicotine (0.6, 2, and 6 μmol/kg) significantly increased the mean arterial pressure in control and BQ 788-pretreated rats, while only a nicotine dose of 2 μmol/kg) increased the mean arterial pressure in JKC 301-pretreated animals. There were no differences in the nicotine-induced changes in heart rate or in the increases in thromboxane B 2 levels among the groups treated with saline, JKC 301 and BQ 788. These results demonstrate that whereas the antagonism of endothelin ET A receptors attenuated the increase in blood pressure after nicotine injections, endothelin ET B receptor antagonism had no such effect. In addition, the antagonism of endothelin ET A or ET B receptors did not affect thromboxane A 2 production after nicotine administration. These findings suggest that endothelin-1 may have a role in the acute effects of nicotine.