Hepatic microvascular regulatory mechanisms. III. Aminergic mechanisms as related to mast cells.

The responses of the hepatic microvasculature to aminergic stimulation were evaluated in Sprague-Dawley rats anesthetized with urethane or pentobarbital. Various concentrations (10(-10)-10(-4) g/ml) of serotonin, histamine or compound 48/80 (a mast cell degranulator) alone or in combination with appropriate blockers were administered topically to the livers of these rats while changes in the microvasculature were measured for a period of 15 min using in vivo microscopic methods. The influence of compound 48/80 on hepatic mast cells was verified by histochemical methods. Histamine induced dilatation of portal venules which was not antagonized by diphenhydramine (H1-blocker) or metiamide (H2-blocker). Constriction was produced by serotonin in sinusoids and by 48/80 in sinusoids and central venules, but not in other parts of the microvasculature. Vasoconstriction was accompanied by enlargement and bulging of the nuclear region of cells lining sinusoids. Concomitantly, platelets and leukocytes adhered to the endothelium of sinusoids, and central and sublobular venules. None of these responses was antagonized by methysergide. Given these results and histochemical demonstration of the release of mast cell constituents following 48/80-induced degranulation, it is hypothesized that the responses in sinusoids and hepatic venules are mediated by serotonin and other mast cell constituents (e.g., prostaglandins, PAF, heparin), but at sites other than histamine and serotonin-specific receptors. These results support the involvement of mast cell constituents in hepatic microvascular regulatory mechanisms.