Organ to organ communication is important in the maintenance of fluid and electrolyte balance and blood pressure (BP) homeostasis. The gastrointestinal tract and the kidney are major organs involved in this process. The natriuresis following the ingestion of a certain amount of sodium, with or without food, may be due to an enterokine, gastrin, secreted by G-cells in the stomach and duodenum and released into the circulation. Abnormalities in stomach sodium sensing and impaired generation of gastrin, gastrin-mediated increase in renal dopamine production, gastrin-mediated natriuresis, or interaction with D1-like receptors cause hypertension. The sodium sensor in the stomach is not known but new data show that sodium sensor in the stomach, specifically in G-cells, is Scn7a. Scn7a colocalizes with gastrin in mouse stomach. Stomach/ duodenum-selective silencing of gastrin impairs the renal response to a salt load and increases BP. Stomach /duodenum selective silencing of Scn7a prevents the increase in serum gastrin following ingestion of sodium (independent of chloride or osmolality) that is also associated with impaired sodium excretion and increased BP in salt-resistant BALB/c mice fed a high sodium diet. However, BP is not increased in patients who have had gastric bypass. Indeed, the high BP can be normalized by gastric bypass. Sleeve gastrectomy actually enhances the increase in plasma gastrin following a mixed meal. By contrast, Roux-en-Y gastric bypass surgery prevents the increase in plasma gastrin following a mixed meal but either type of bypass surgery increases plasma levels of natriuretic enterokines, such as GLP-1. GLP- 1 from L-cells that is secreted via gastrin-dependent and -independent (e.g. sodium) mechanisms may also participate in this gastro-renal communication. Therefore, this competitive renewal will test the overall hypothesis that the sodium sensor that is responsible for increasing the secretion of gastrin from stomach G-cells and GLP-1 from intestinal L-cells, in response to an oral sodium load, is the sodium channel, Scn7a. Gastrin, acting on renal CCKBR, GLP-1, acting on its receptor GLP-1R, also in the kidney, and dopamine produced in the kidney, acting on renal D1R, interact to negatively regulate renal sodium transport and keep the BP in the normal range.