Endothelin ET(A) receptor antagonism attenuates the pressor effects of nicotine in rats.
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 micromol/kg) in anesthetised rats. Nicotine (0.6, 2, and 6 micromol/kg) significantly increased the mean arterial pressure in control and BQ 788-pretreated rats, while only a nicotine dose of 2 micromol/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.
Tanus-Santos
J E
JE
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), P.O. Box 6111, 13081-970, SP, Campinas, Brazil.
Sampaio
R C
RC
Hyslop
S
S
Franchini
K G
KG
Moreno
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013929:Thromboxane B2 / Q000097:blood
D065128:Endothelin Receptor Antagonists; D018722:Nicotinic Agonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013929:Thromboxane B2; D009538:Nicotine