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Reduced RhoA activity mediates the acute alcohol intoxication‐induced reduction of lymphatic myogenic constriction independently of cytosolic [Ca2+]
Author(s) -
Souza-Smith Flavia Moreira,
Kurtz Kristine K,
Breslin Jerome W
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.677.8
Subject(s) - rhoa , chemistry , lymphatic system , constriction , calcium , endocrinology , mesenteric arteries , medicine , vasoconstriction , contraction (grammar) , alcohol , anatomy , biochemistry , pathology , signal transduction , artery
The RhoA‐ROCK pathway is involved in [Ca 2+ ]‐independent regulation of MLC20 phosphorylation through its inhibition of MLCP and, thus, the regulation of smooth muscle contraction. We previously showed that alcohol modulates the intrinsic contractile cycle of mesenteric lymphatics that provides the driving force for lymph flow. We hypothesized that either calcium signaling or sensitivity mediate the changes in intrinsic lymphatic pumping caused by alcohol. Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheter. Isovolumic administration of water (vehicle) served as control. Mesenteric lymphatics were isolated, cannulated and loaded with Fura‐2 AM. Calcium measurements were performed at a basal intraluminal pressure of 2 cm H 2 O and during pressure steps to 4, 6, 8, 10 and 12 cm H 2 O. RhoA activity was determined using a G‐LISA™ assay. With each pressure step [Ca 2+ ] gradually increased for both control and alcohol, however myogenic constriction was impaired in the alcohol group. RhoA activity was significantly reduced in lymphatics from the alcohol group compared with controls. Reduced myogenic constriction from alcohol treated lymphatics is due to reduction on [Ca 2+ ] sensitivity likely mediated by RhoA signaling.