Quantitation of rat hepatic stellate cell contraction: stellate cells’ contribution to sinusoidal resistance

Abstract

Although it has been hypothesized that contraction of hepatic stellate cells (HSC) regulates blood flow by modulating sinusoidal resistance, neither HSC contraction nor relaxation has been directly quantitated. To test this hypothesis, a force transducer was employed to directly measure the magnitude and rate of contraction and relaxation by primary rat HSC (4.7 × 105 ± 0.2 × 105 cells) cultured within a collagen gel. Serial exposures to 10% fetal bovine serum stimulated 81 ± 14 and 82 ± 10 dyn of contractile force, respectively. Subsequent stimulation with 2 nM endothelin-1 (ET-1) resulted in the development of 185 ± 25 dyn of force. Contractions began within 10 s of ET-1 stimulation, and the half time of maximal force development was <5 min. Removal of agonist resulted in complete or nearly complete relaxation within 45 min. These results suggest that the magnitude and rate of HSC contraction and relaxation are capable of modulating blood flow via sinusoidal constriction.