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Atrial natriuretic peptide antagonizes endothelin‐induced calcium increase and cell contraction in cultured human hepatic stellate cells
Author(s) -
Görbig M. Nieves,
Ginès Pere,
Bataller Ramón,
Nicolás Josep M.,
GarciaRamallo Eva,
Tobías Ester,
Titos Esther,
Rey María Jes,
Clària Joan,
Arroyo Vicente,
Rodés Juan
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300201
Subject(s) - atrial natriuretic peptide , medicine , receptor , endocrinology , cyclic guanosine monophosphate , endothelin receptor , endothelin 1 , hepatic stellate cell , biology , intracellular , chemistry , microbiology and biotechnology , nitric oxide
Hepatic stellate cells (HSCs) participate in the regulation of hepatic microcirculation and have receptors for many vasoconstrictor factors. It is unknown whether HSCs have receptors for circulating vasodilators such as atrial natriuretic peptide (ANP). This study investigated the presence of ANP receptors in human HSCs and whether ANP antagonizes the effects of endothelin‐1 in these cells. ANP receptors were assessed by binding and cross‐linking studies, reverse‐transcriptase polymerase chain reaction (PCR), and measuring intracellular cyclic guanosine monophosphate concentration. Intracellular calcium concentration ([Ca 2+ ] i ) and cell contraction were measured in individual cells loaded with fura‐2 using a morphometric method. Binding and cross‐linking affinity experiments showed the existence of ANP receptors in human HSCs. PCR products with the expected length were obtained for guanylate cyclase A receptor, the physiological receptor of ANP, both in quiescent and activated human cells. ANP induced a dose‐dependent increase in intracellular cyclic guanosine monophosphate concentration and blunted the increase in [Ca 2+ ] i elicited by endothelin‐1. Most importantly, ANP markedly reduced cell contraction induced by endothelin‐1. HSCs isolated from rats with carbon tetrachloride‐induced cirrhosis showed a higher number of ANP receptors compared with HSCs isolated from normal rats, indicating that in vivo activation of HSCs is associated with an up‐regulation of ANP receptors. These results indicate that human HSCs have receptors for ANP, the activation of which reduces the effects of endothelin‐1 on [Ca 2+ ] i and cell contraction. ANP could participate in regulating the contractility of HSCs by antagonizing the effect of vasoconstrictors.