Effect of adrenomedullin on hepatic pericytes (stellate cells) of the rat

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Abstract
When hepatic stellate cells (Ito cells, fat-storing cells) were incubated with adrenomedullin, they underwent relaxation as monitored by the silicone-rubber membrane method; 43%, 65% and 87% of stellate cells relaxed 5, 10 and 20 min, respectively, after addition of 10−6 M adrenomedullin. Adrenomedullin also triggered the dissociation of F-actin and induced transformation of stellate cells to dendritic cell-like structure. When incubated with 10−6 M of adrenomedullin for 30 min, cellular levels of cAMP increased from the basal value of 10.2 ± 1.4 to 107 ± 2.8 pmol/2 × 105 cells without affecting cGMP levels. The reaction occurred dose-dependently and was inhibited by an antagonist of calcitonin gene-related peptide. Adrenomedullin had negligible effects on DNA and protein synthesis in proliferating stellate cells. Thus, adrenomedullin is a potent relaxing peptide to hepatic stellate cells and may contribute to the regulation of sinusoidal microcirculation