Gastrin And D₁Dopamine Receptor Interact To Induce Natriuresis And Diuresis

Objective Oral NaCl intake produces stronger natriuresis and diuresis than venousinfusion 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 andtaken-up by the renal proximal tubule (RPT) cells. We hypothesize that gastrin interactswith dopamine receptors in kidney, resμlting in synergistically increased sodiμm excretion.The impaired interaction might be involved in the pathogenesis of essential hypertension(EH).Method Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and RPTcells were stimμlated or blocked through D1-like dopamine and gastrin receptors to observeNa+-K+-ATPase activity and natriuresis.Result 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, effecthereinbefore of Fenoldopam, a D1-like receptor agonist, was blocked by D1-like receptorantagonist, SCH23390, indicating gastrin and fenoldopam exert natriuretic and diureticeffect through individual receptors. Lower dosages of gastrin or Fenoldopam failed toinduce natriuresis and diuresis alone, while putting together induced the effects. Theabove-mentioned effects were lost in SHRs. Natriuresis and diuresis was partially blockedby SCH23390or CI-988, indicating the interaction between gastrin and D1-like receptor.Stimulation of either receptor increased the expression of the other and inhibitedNa+-K+-ATPase activity, while the inhibitory effect of Na+-K+-ATPase activity was partiallyblocked throμgh its corresponding receptors due to respective existence of SCH23390andCI-988. Conclusion It indicated the synergistic effect between gastrin and D1-like receptorwould increase the sodium excretion in WKY rats; the impaired interaction might beinvolved in the pathogenesis of hypertension.