Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

NaCl hyperosmolarity increases intestinal blood flow during food absorption due in large part to increased NO production. We hypothesized that in vivo, sodium ions enter endothelial cells during NaCl hyperosmolarity as the first step to stimulate an increase in intestinal endothelial NO production. Perivascular NO concentration ([NO]) and blood flow were determined in the in vivo rat intestinal microvasculature at rest and under hyperosmotic conditions, 330 and 380 mosM, respectively, before and after application of bumetanide (Na+-K+-2Cl− cotransporter inhibitor) or amiloride (Na+/H+ exchange channel inhibitor). Suppressing amiloride-sensitive Na+/H+ exchange channels diminished hypertonicity-linked increases in vascular [NO], whereas blockade of Na+-K+-2Cl− channels greatly suppressed increases in vascular [NO] and intestinal blood flow. In additional experiments we examined the effect of sodium ion entry into endothelial cells. We proposed that the Na+/Ca2+ exchanger extrudes Na+ in exchange for Ca2+, ...