TY - JOUR
T1 - Altered central TRPV4 expression and lipid raft association related to inappropriate vasopressin secretion in cirrhotic rats
AU - Carreño, Flávia Regina
AU - Ji, Lisa L.
AU - Cunningham, J. Thomas
PY - 2009/2
Y1 - 2009/2
N2 - Inappropriate vasopressin (AVP) release causes dilutional hyponatremia in many pathophysiological states such as cirrhosis. The central molecular mechanisms that mediate inappropriate AVP release are unknown. We tested the hypothesis that changes in the expression or trafficking of TRPV4 in the central nervous system may contribute to inappropriate AVP release in the bile duct ligation (BDL) model of cirrhosis in the rat. Four weeks after surgery, BDL rats demonstrated significantly increased plasma vasopressin and plasma renin activity (PRA), hypervolemia, and decreased plasma osmolality. These effects were blocked by providing BDL rats with 2% saline to drink for 15 days. TRPV4 protein expression was significantly increased in brain punches from BDL rats containing the supraoptic nucleus (SON) of the hypothalamus (100% ± 11 to 157% ± 4.8), and this effect was blocked in BDL rats given saline. Immunohistochemistry demonstrated a significant increase in TRPV4-positive cells and the percentage of AVP neurons that also were TRPV4-positive in the SON of BDL rats. In the hypothalamus of BDL rats, TRPV4 lipid raft association increased compared with sham (from 100% ± 2.1 to 326.1% ± 16). This effect was significantly attenuated in BDL rats given 2% saline to drink (174% ± 11). In the brain stem, TRPV4 lipid raft association was reduced by BDL and inversely related to plasma AVP and PRA. We speculate that changes in TRPV4 expression and compartmentalization within lipid rafts could contribute to a feedforward mechanism related to AVP release in cirrhosis.
AB - Inappropriate vasopressin (AVP) release causes dilutional hyponatremia in many pathophysiological states such as cirrhosis. The central molecular mechanisms that mediate inappropriate AVP release are unknown. We tested the hypothesis that changes in the expression or trafficking of TRPV4 in the central nervous system may contribute to inappropriate AVP release in the bile duct ligation (BDL) model of cirrhosis in the rat. Four weeks after surgery, BDL rats demonstrated significantly increased plasma vasopressin and plasma renin activity (PRA), hypervolemia, and decreased plasma osmolality. These effects were blocked by providing BDL rats with 2% saline to drink for 15 days. TRPV4 protein expression was significantly increased in brain punches from BDL rats containing the supraoptic nucleus (SON) of the hypothalamus (100% ± 11 to 157% ± 4.8), and this effect was blocked in BDL rats given saline. Immunohistochemistry demonstrated a significant increase in TRPV4-positive cells and the percentage of AVP neurons that also were TRPV4-positive in the SON of BDL rats. In the hypothalamus of BDL rats, TRPV4 lipid raft association increased compared with sham (from 100% ± 2.1 to 326.1% ± 16). This effect was significantly attenuated in BDL rats given 2% saline to drink (174% ± 11). In the brain stem, TRPV4 lipid raft association was reduced by BDL and inversely related to plasma AVP and PRA. We speculate that changes in TRPV4 expression and compartmentalization within lipid rafts could contribute to a feedforward mechanism related to AVP release in cirrhosis.
KW - Hypothalamus
KW - Lipid rafts
KW - Renin-angiotensin
KW - Supraoptic nucleus
UR - http://www.scopus.com/inward/record.url?scp=61949445166&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.90460.2008
DO - 10.1152/ajpregu.90460.2008
M3 - Article
C2 - 19091909
AN - SCOPUS:61949445166
SN - 0363-6119
VL - 296
SP - R454-R466
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 2
ER -