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Background/Aims: Angiotensin II (ANG II) decreases dopamine (DA) uptake in renal cortex activating AT₁ receptors. We investigated the signaling pathways that mediate this action and the incidence of DA-ANG II interaction on renal Na⁺,K⁺-ATPase activity. Methods: ANG II effects on [³H]-DA uptake and Na⁺,K⁺-ATPase were measured in samples from the outer renal cortex of Sprague-Dawley rats. Results: Inhibition of the phospholipase C (PLC) pathway blunted ANG II inhibitory effects on [³H]-DA uptake, since U-73122, 2-APB, TMB-8, chelerythrine and KN-93 (PLC, IP₃-dependent Ca²⁺ release channels, IP₃ receptors, protein kinase C and CaM kinase II inhibitors, respectively) each one blocked ANG II effects. Inhibition of adenylate cyclase pathway did not modify ANG II inhibitory effects on DA uptake. ANG II effects on [³H]-DA uptake were able to modify Na⁺,K⁺-ATPase activity in carbidopa-treated rats. Exogenous DA decreased while ANG II increased the enzyme activity. Neither the addition of DA together with ANG II, nor the extraneuronal DA uptake blocker hydrocortisone altered ANG II stimulatory effects on Na⁺,K⁺-ATPase activity, but hydrocortisone blocked the inhibitory effects of exogenous DA. Conclusion: Stimulation of renal AT₁ receptors by ANG II signals through the PLC pathway to inhibit extraneuronal DA uptake. DA and ANG II act through a common pathway involving reversible renal tubular Na⁺,K⁺-ATPase deactivation and activation, respectively. In addition, ANG II by itself is able to stimulate renal Na⁺,K⁺-ATPase activity.

Background/Aims: Dopamine (DA) uptake inhibition in the renal cortex, elicited by angiotensin II (ANG II), is mediated by AT₁ receptors and signals through the phospholipase C pathway and activation of protein kinase C and CaM-kinase II. By this indirect way, ANG II stimulates renal Na⁺,K⁺-ATPase activity through DA intracellular reduction. In the present work, we continued to study different aspects of renal DA metabolism in DA-ANG II interaction, such as DA synthesis, release, catabolism and turnover. Methods: ANG II effects on DA synthesis, release, catabolism and turnover were measured in samples from the outer renal cortex of Sprague-Dawley rats. Results: ANG II reduced renal aromatic acid decarboxylate activity without affecting basal secretion of DA or its KCl-induced release. Moreover, ANG II enhanced monoamine oxidase activity without altering catechol-o-methyl transferase activity and increased DA turnover. Conclusion: Current results as well as previous findings show that ANG II modifies DA metabolism in rat renal cortex by reducing DA uptake, decreasing DA synthesis enzyme activity and increasing monoamine oxidase activity, and DA turnover. Together, all these effects may reduce DA accumulation into renal cells and decrease its endogenous content and availability. This would prevent D1 receptor recruitment and stimulation, while diminishing DA inhibition of Na⁺,K⁺-ATPase activity and stimulating sodium reabsorption.