Sodium-deprived rat distal colon epithelial response to acute hypoxia and reoxygenation.
In normal rat distal colon isolated mucosa, basal short-circuit current (Isc) is mostly due to chloride secretion. Isc is depressed by a brief (5 min) acute hypoxia and overshoots above baseline during reoxygenation. Sodium deprivation raises serum aldosterone levels and leads to expression of functional epithelial sodium channels which are amiloride-sensitive. Thus, in sodium-deprived rats (SDRs) Isc is dependent on electrogenic sodium absorption. Since the ion primarily responsible for the Isc is different in each functional condition, it is not known whether hypoxia and reoxygenation affect SDRs epithelial response in the same way as in normal rats. Therefore the electrical behavior of isolated mucosa preparations from normal and SDRs was studied in an Ussing chamber, and the effect of the epithelial sodium channel blocker, amiloride sensitive, basal Isc than controls. Their response to hypoxia (expressed as a fraction of basal Isc) was similar to controls but upon reoxygenation their recovery was incomplete. SDRs response to hypoxia was not affected by amiloride at any concentration tested. However, post-hypoxic recovery was modified by amiloride in a concentration-dependent way: it was incomplete at 10(-8) M, complete at 10(-6) M, and at 10(-4) M it overshooted above baseline values. Therefore, in sodium-deprived rats, sodium channel blockade reverts the pattern of blunted recovery to the overshooting pattern seen normal rats. These results may be explained by two non-mutually exclusive hypotheses: Epithelial sodium channel blockade in sodium-deprived rats might (1) unmask a basal chloride conductance, and (2) interfere with a negative interaction between sodium chloride conductances.
Saraví
F D
FD
Cátedra de Física Biológica, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Saldeña
T A
TA
Tonn
E F
EF
Cincunegui
L M
LM
Carra
G E
GE
Ibáñez
J E
JE
D000450:Aldosterone / Q000097:blood*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D003106:Colon / Q000187:drug effects / Q000503:physiopathology*; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000172:deficiency*
D004232:Diuretics; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium