Hepatic microvascular regulatory mechanisms. IX. Effects of compound 48/80 on endotoxin-induced changes in...

Changes in hepatic microvasculature and systemic arterial blood pressure were measured in anesthetized male Sprague-Dawley rats pretreated with intraperitoneal injections of compound 48/80 for 5 days. Each rat was studied for 1 hr after receiving an endoportal infusion of 15 mg per kg b.w. E. coli endotoxin or sterile saline solution (control) on the sixth day. Administration of compound 48/80 for 5 days released mast cell mediators thereby depleting intracellular constituents such as serotonin and producing a 52% decrease in the number of these cells counted in portal areas of the liver. All compound 48/80-injected rats remained normotensive during the 60 min period of experimentation. However, in vivo microscopy revealed that pretreatment for 5 days abolished endotoxin-induced decreases in the internal diameters (D) of centrilobular sinusoids and constriction at the inlet of periportal and the outlet of centrilobular sinusoids. In contrast, cellular blood flow velocities (V) were elevated at the inlet within 5 min and at the outlet by 5, 50 and 60 min when compared to control. This increase resulted in enhanced relative rates of volumetric flow (Q) within these segments. Exacerbation of platelet and leukocyte adherence to the wall of the microvasculature also was evident. Based upon these results it is suggested that mast cell-derived mediators such as serotonin maintain (Q) within hepatic lobules up to 1 hr following the onset of endotoxemia. Such autoregulation is hypothesized to be mediated by mast cell-induced modulation of microvascular (D) in response to endotoxin-elicited changes in (V).