Roles of endothelin-1 in endotoxin-induced microcirculatory disturbance in rat small intestine. Miura, Soichiro, Dai Fukumura, Iwao Kurose, Hajime Higuchi, Hiroyuki Kimura, Yoshikazu Tsuzuki, Takeharu Shigematsu, Jing-Yan Han, Masaharu Tsuchiya, and Hiromasa Ishii. Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan
APStracts 3:0051G, 1996.
The major objective of this study was to investigate whether endothelin-1(ET-1) plays a significant role in endotoxin-induced microcirculatory disturbances of the intestinal mucosa. Submucosal microvessels of the rat ileum were observed by intravital microscopy with a high-speed video camera system. Preceding the apparent intestinal mucosal damage, red blood cell (RBC) velocity was significantly decreased 30 min after endotoxin treatment in both arterioles and venules. The number of leukocytes sticking to submucosal venules was significantly increased at 30 min. BQ-123, an ETA receptor antagonist, significantly attenuated the decrease in RBC velocity and also prevented an increase in leukocyte sticking as well as the subsequent mucosal damage induced by endotoxin. The ET-1 concentrations began to be elevated in plasma at 15 min and in the mucosa at 30 min, and subsequently further increased in a time -dependent manner. A significant decrease in calcium-dependent nitric oxide synthase activity, and significant increases in the concentration of platelet activating factor were demonstrated in the intestinal mucosa after endotoxin treatment. BQ-123 also significantly attenuated these changes. We concluded that the increased ET-1 production in intestinal mucosa induced by endotoxin stimulation could lead to leukocyte sticking and decreased RBC velocity in the intestinal microcirculatory beds via ETA receptors, which is closely related to increased production of platelet activating factor and decreased synthesis of constitutive nitric oxide. 

Received 24 April 1995; accepted in final form 20 February 1996.
APS Manuscript Number G168-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 March 96