The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Na+-K+ ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Rabbit polyclonal to COXiv. Na+-K+ ATPase activity in WKY cells. In SHR cells the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na+-K+ ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na+-K+ ATPase activity in SHR cells. This was confirmed in vivo; pre-treatment with PD128077 for one week augmented the anti-hypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension. and/or a failure to respond appropriately to signals that decrease sodium transport. Ion transport in the RPT and thick ascending Moxalactam Sodium limb of Henle which is increased in essential hypertension is regulated by numerous hormones and humoral factors including angiotensin II and dopamine2 3 Paracrine regulation of sodium reabsorption in the proximal tubule by the renin-angiotensin system occurs via several angiotensin receptor subtypes (AT1 and AT2)2 3 Moxalactam Sodium The major effect of angiotensin II on sodium transport is stimulatory via AT1 receptors. In the adult spontaneously hypertensive rat (SHR) renal AT1 receptor expression is similar to that found in normotensive rats but the AT1 receptor-mediated sodium reabsorption is increased in the RPT of SHRs4 5 Proximal tubule fluid reabsorption/transport (NHE3 activity) is higher in SHRs than WKY rats at 5 weeks of age but may not be always increased at 12 weeks of age6-9. The ability of an angiotensin converting enzyme inhibitor to decrease proximal tubule fluid reabsorption has been reported to be greater in younger than older SHRs indicating increased sensitivity to endogenous angiotensin II in the young SHR6 that may be related to increased renal AT1 receptors in the young5. However the increased sensitivity of RPT transport to angiotensin II in the adult SHR4 is not due to increased renal expression of AT1R5. The dopaminergic system also exerts a paracrine regulatory role on renal sodium transport in the RPT2 3 Dopamine receptors like AT1 receptor are expressed in the brush border and basolateral membranes of the RPT3. In contrast to the stimulatory effect of the AT1 receptor on sodium transport in the RPT the major consequence of the activation of dopamine receptors is inhibition of sodium transport2 3 According to their structure and pharmacology dopamine receptors are classified into D1-like (D1 and D5 receptors) and D2-like (D2 D3 and D4 receptors) subtypes. D1-like receptors stimulate while D2-like receptors inhibit cAMP production3. Increasing pieces of evidence show interaction between dopamine and angiotensin II receptors2. Our previous study also showed a negative interaction between the D3 and AT1 receptors wherein activation of the D3 receptor inhibits AT1 receptor expression and function in RPT cells10. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal AT1 receptor expression11. The hypotensive effect of a bolus intravenous injection of the AT1 receptor antagonist losartan lasted longer in D4 receptor gene deficient mice than their wild-type littermates11. In the kidney the D4 receptor is expressed in the proximal and distal convoluted tubules collecting duct and thick ascending limb of Henle Moxalactam Sodium in some species12. Because the RPT is responsible for about 70% of renal sodium reabsorption we hypothesize that activation of the D4 receptor can inhibit AT1 receptor expression and function in the RPT from Wistar-Kyoto (WKY) rats and their interaction may be aberrant in cells from SHRs. In order to test Moxalactam Sodium the above hypothesis we studied D4 receptor and AT1 receptor interaction in immortalized RPT cells from WKY and SHRs. Meanwhile the anti-hypertensive and natriuretic effect of AT1 receptor blocker with or without D4 receptor agonist in SHRs and WKY rats were also measured in vivo. These RPT cells behave similarly to freshly.