LB02.04

Objective: Oral NaCl intake produces stronger natriuresis and diuresis than venous infusion of the same amount NaCl, indicating the potential existence of renal-gastric axis. Gastrin, from gastrointestinal tract, is dominant one due to its natriuretic effects and taken-up by the renal proximal tubule (RPT) cells. We hypothesize that gastrin interacts with dopamine receptors in kidney, resμlting in synergistically increased sodiμm excretion. The impaired interaction might be involved in the pathogenesis of essential hypertension (EH).Design and method: Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and RPT cells were stimμlated or blocked through D1-like dopamine and gastrin receptors to observe Na +-K +-ATPase activity and natriuresis. Results: Gastrin infusing WKY rats via renal artery induced natriuresis and diuresis, which was blocked in the presence of CI-988, a gastrin receptor blocker. Similarly, effect hereinbefore of Fenoldopam, a D1-like receptor agonist, was blocked by D1-like receptor antagonist, SCH23390, indicating gastrin and fenoldopam exert natriuretic and diuretic effect through individual receptors. Lower dosages of gastrin or Fenoldopam failed to induce natriuresis and diuresis alone, while putting together induced the effects. The above-mentioned effects were lost in SHRs. Natriuresis and diuresis was partially blocked by SCH23390 or CI-988, indicating the interaction between gastrin and D1-like receptor. Stimulation of either receptor increased the expression of the other and inhibited Na+-K+-ATPase activity, while the inhibitory effect of Na+-K+-ATPase activity was partially blocked throμgh its corresponding receptors due to respective existence of SCH23390 and CI-988. Conclusions: It indicated the synergistic effect between gastrin and D1-like receptor would increase the sodium excretion in WKY rats; the impaired interaction might be involved in the pathogenesis of hypertension.