Stimulation of constitutive nitric oxide uniquely and compensatorily regulates intestinal epithelial cell brush border membrane Na absorption

In the mammalian small intestine, sodium is primarily absorbed by Na + /H + exchange ( NHE 3) and Na‐glucose cotransport ( SGLT 1) in the brush border membrane ( BBM ) of villus cells. However, how enhanced cellular constitutive nitric oxide ( cNO ) may affect NHE 3 and SGLT 1 remains unclear. Both in vivo in rabbit intestinal villus cells and in vitro IEC ‐18 cells, administration of NO donor, GSNAP , modestly increased cNO . GSNAP stimulated SGLT 1 in villus and IEC ‐18 cells. The mechanism of stimulation was secondary to an increase in the affinity of SGLT 1 for glucose. The change in SGLT 1 was not secondary to altered Na‐extruding capacity of the cell since Na + /K + ‐ ATP ase was decreased by GSNAP treatment. In contrast, GSNAP inhibited NHE 3 activity in villus cell BBM . The mechanism of NHE 3 inhibition was secondary to reduced BBM transporter numbers. These studies demonstrated that the physiological increase in cNO uniquely regulates mammalian small intestinal NHE 3 and SGLT 1 to maintain Na homeostasis.