期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 137, 期 2, 页码 213-220出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjp.0704850
关键词
LPS; endotoxin; rat vascular mesenteric bed; mesenteric arteries; aorta; membrane potential; calcium-dependent potassium channel; iberiotoxin; endothelin
1 The direct and endothelium-dependent effects of lipopolysaccharide (LPS) were investigated on resistance and conductance arteries from normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats. 2 In both NWR and SHR, LPS induced dose-dependent relaxations of the mesenteric vascular bed, which were inhibited by L-NNA in SHR but not in NWR. Iberiotoxin (IBTX) inhibited the responses to LPS in both groups, indicating the participation of high conductance Ca2+-dependent K+ channels. 3 In mesenteric artery rings, the resting membrane potentials and the hyperpolarizing responses of NWR to LPS did not differ in endothelized and denuded preparations but L-NNA inhibited the responses only in endothelized rings. These responses were reduced by bosentan, suggesting that endothelin release may mask a possible hyperpolarizing response to LPS. The hyperpolarizing responses to LPS were blocked by IBTX in both endothelized and de-endothelized NWR rings. In the SHR only intact rings showed hyperpolarization to LPS, which was inhibited by IBTX and by L-NNA. 4 In SHR aortic endothelized or denuded rings, LPS induced hyperpolarizing responses which, in endothelized rings, were partially blocked by L-NNA, by IBTX or by glibenclamide, but totally abolished by IBTX plus glibenclamide. No response to LPS was observed in NWR aortic rings. 5 Our results indicate that LPS activates large conductance Ca2+-sensitive K+ channels located in the smooth muscle cell membrane both directly and indirectly, through NO release from the endothelium in NWR, whereas NO is the major mediator of the LPS responses in SHR resistance vessels.
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