Effects of Angiotensin II on Renal Dopamine Metabolism: Synthesis, Release, Catabolism and Turnover

Abstract

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.

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage

“…Por otro lado, se ha descripto que la Ang II inhibe la captación renal de DA mediante estimulación de los receptores AT 1 , en un mecanismo que implica la vía de señalización de PLC, con generación de los segundos mensajeros inositol 1,4,5-trifosfato (IP3) y diacilglicerol (DAG), liberación de Ca 2+ intracelular y activación de PKC y calmodulina quinasa II (CaMKII) (Choi y col., 2006;Choi y col., 2009). Adicionalmente, la Ang II reduce la actividad de la DCAA y estimula la actividad de la MAO, reduciendo la síntesis y aumentando el catabolismo de la DA renal (Choi y col., 2010). En su conjunto, todos estos efectos previenen la acumulación de DA en las células del TP, resultando en una disminución de la biodisponibilidad de la amina en el interior de la célula y en la luz tubular de la nefrona.…”

Human GRK4γ 142V Variant Promotes Angiotensin II Type I Receptor–Mediated Hypertension via Renal Histone Deacetylase Type 1 Inhibition

“…Similarly, short-term treatment with AngII diminishes D 1 R at the plasma membrane in the WKY, but not SHR, although chronic treatment results in increased D 1 R expression (37), possibly as compensation. AngII also decreases dopamine uptake and dopamine synthesis in the renal cortex (38). Simultaneous activation of D 1 R and AT 1 R can increase or decrease Na + ,K + -ATPase activity that is dependent on the intracellular sodium concentration, an increase of which favors D 1 R action (39).…”

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“…One of the most investigated subjects related to the pathophysiology of DN is the renin-angiotensin system. Regardless of their hemodynamic effects, it has been reported that Ang II contributes to the development and progression of renal damage through the AT1 receptor in diabetic patients [17][18][19][20]. The activity of monoamine oxidases, especially MAO-A, is increased by Angiotensin II through the AT1 receptor in kidneys [21].…”

“…In addition, Angiotensin II increases MAO activity in rat kidneys by activating AT1 receptor. Diabetic animal models, clinical trials, and meta-analysis have clearly demonstrated the effectiveness of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers to improve glomerular and tubulointerstitial damage, reduce proteinuria, and decrease progression of chronic kidney disease [18][19][20][21]. According to the above description, MAO levels might be found increased in DN and this state might contribute to reducing the natriuretic effect of dopamine and to unbalanced cell redox state.…”