Portal hypertension induces sodium channel expression in colonocytes from the distal colon of the rat.
Cellular mechanisms for Na(+) retention in portal hypertension are undefined, but epithelial Na(+) channels (ENaC) may be involved. Under high-salt diet, ENaC are absent from distal colon of rat but can be induced by mineralocorticoids such as aldosterone. Presence of rat ENaC was determined by amiloride inhibition of (22)Na(+) uptake in surface colonocytes 7 and 14 days after partial portal vein ligation (PVL) or sham surgery. At both times, uptake inhibition was significantly increased in PVL rats. Presence of mRNA transcripts, determined by RT-PCR, demonstrated that channel alpha- and gamma-subunits were similarly expressed in both groups but that beta-subunit mRNA was increased in PVL rats. This confirms that there was induction of rat ENaC and indicates that beta-subunit has a regulatory role. Urinary Na(+) was decreased for 3 days after PVL but was not different at other times, and serum aldosterone levels were elevated at 7 days, at a time when urinary Na(+) output was similar to that of sham-operated rats. We conclude that PVL leads to induction of ENaC in rat distal colon. An increase in aldosterone levels may prevent natiuresis and is probably one of several control mechanisms involved in Na(+) retention in portal hypertension.
Fraser
G M
GM
Department of Gastroenterology, Rabin Medical Center, Beilinson Campus and Sackler Faculty of Medicine, University of Tel-Aviv, Petach Tikva 49100, Israel. gfraser@post.tau.ac.il
Blendis
L M
LM
Smirnoff
P
P
Sikular
E
E
Niv
Y
Y
Schwartz
B
B
D000450:Aldosterone / Q000097:blood; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000166:cytology* / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D015870:Gene Expression / Q000502:physiology; D006975:Hypertension, Portal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008026:Ligation; D011169:Portal Vein; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000652:urine; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics
D004232:Diuretics; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D015222:Sodium Channels; D012979:Sodium Radioisotopes; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium