ENDOTHELIUM-DEPENDENT MICROVASCULAR RESPONSES TO ACTIVATED COMPLEMENT

Infusion of Escherichia coli bacteria to cause high cardiac output bac teremia produces a differential microvascular response with constricti on of large arterioles and dilation of small arterioles in skeletal mu scle of rats. An important component to host-defense mechanisms during bacteremia is activation of the complement system. One part of this s tudy explored the possibility that microvascular responses to bacterem ia could be mediated by activation of the alternative complement casca de to alter skeletal muscle blood flow during sepsis. Complement activ ation by iv zymosan into unanesthetized (decerebrate) Sprague-Dawley r ats caused constriction of large arterioles and dilation of small arte rioles in cremaster muscle, while cardiac output stayed normal or was elevated. These microvascular responses mimic those during bacteremia, suggesting that components of the complement system mediate skeletal muscle microcirculatory responses to live E. coli sepsis. The vasodila tion response of small arterioles in skeletal muscle during bacteremia is endothelium-dependent and is mediated at least partially by endoth elial-derived relaxing factor (EDRF). Complement activation gives prod ucts which interact with endothelial cells. Thus, a second part of thi s study explored the role of EDRF in the vasodilation of skeletal musc le small arterioles during activation of the alternate complement path way. Blockade of EDRF action by hydroquinone totally abolished small a rteriole dilation and large arteriole constriction responses to comple ment activation by zymosan infusion. (C) 1994 Academic Press, Inc.