RESUMO
BACKGROUND/AIMS: Dopamine (DA) uptake inhibition in the renal cortex, elicited by angiotensin II (ANG II), is mediated by AT(1) 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.
Assuntos
Angiotensina II/administração & dosagem , Angiotensina II/metabolismo , Dopamina/metabolismo , Rim/metabolismo , Animais , Relação Dose-Resposta a Droga , Rim/efeitos dos fármacos , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Metabolismo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND/AIMS: The present study was designed to evaluate the effects of a salt load combined with exogenous low nonhypertensive angiotensin II (Ang II) doses on Ang II intrarenal regulation. METHODS: Sprague-Dawley rats were infused with Ang II nonhypertensive doses (0.1 microg.kg(-1).h(-1) and 5 microg.kg(-1).h(-1)) and saline overload (Na 0.5 M, Na 1.0 M and Na 1.5 M) for 2 h (0.04 ml.min(-1)). Sodium tubular reabsorption, sodium urinary excretion and mean arterial pressure (MAP) were measured. Ang II was evaluated in the kidneys by immunohistochemistry. RESULTS: Ang II levels in glomeruli and vessels were exacerbated when sodium load and Ang II were given simultaneously, independently of MAP elevation. In tubules, Ang II staining in the presence of sodium overload was greater in the Ang 0.1 groups than in the Ang 5 groups. Compared with the controls, sodium tubular reabsorption rose in the Ang 0.1-Na 0.5 and Ang 0.1-Na 1 groups and sodium urinary excretion decreased in the Ang 5-Na 0.5 and Ang 5-Na 1 groups. MAP increased in the Ang 5-Na 1 and Ang 5-Na 1.5 groups. CONCLUSION: We conclude that local renal Ang II levels were upregulated when acute sodium overload and nonhypertensive Ang II doses were administered simultaneously in normal rats, independently from blood pressure and glomerular function changes.
Assuntos
Angiotensina II/metabolismo , Angiotensina II/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Sódio/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular/efeitos dos fármacos , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Sódio/urina , Vasoconstritores/farmacologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
BACKGROUND/AIMS: Angiotensin II (ANG II) decreases dopamine (DA) uptake in renal cortex activating AT(1) 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 [(3)H]-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 [(3)H]-DA uptake, since U-73122, 2-APB, TMB-8, chelerythrine and KN-93 (PLC, IP(3)-dependent Ca(2+) release channels, IP(3) 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 [(3)H]-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 AT(1) 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.
Assuntos
Angiotensina II/metabolismo , Dopamina/metabolismo , Córtex Renal/enzimologia , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/metabolismo , Inibidores de Adenilil Ciclases , Adenilil Ciclases/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dopaminérgicos/farmacologia , Inibidores Enzimáticos/farmacologia , Receptores de Inositol 1,4,5-Trifosfato/antagonistas & inibidores , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Córtex Renal/efeitos dos fármacos , Masculino , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismoRESUMO
Since renal natriuretic peptide urodilatin (URO) exerts similar natriuretic and diuretic actions to those of atrial natriuretic factor (ANF), we hypothesized that URO regulates renal dopamine (DA) availability, contributing to Na(+), K(+)-ATPase inhibition. URO (1-100 nM) increased (3)H-DA uptake in outer and juxtamedullar renal cortex and medulla slices from Sprague Dawley rats. Hydrocortisone blocked URO-stimulated DA uptake, demonstrating that DA uptake was extraneuronal. The natriuretic peptide receptor type A antagonist anantin blocked URO-dependent increase of (3)H-DA uptake, while the natriuretic peptide receptor type C agonist ANF 4-23-amide did not modify URO effect on DA uptake, suggesting that only natriuretic receptors type A are involved. Co-incubation of URO and ANF did not show additive effects on DA uptake. To test whether URO effect involves changes in Na(+), K(+)-ATPase activity we performed experiments in renal cortex samples of rats with DA synthesis and neuronal uptake inhibited by carbidopa and nomifensine, respectively. When endogenous DA synthesis was inhibited, URO or DA decreased Na(+), K(+)-ATPase activity. URO and DA added together, further decreased Na(+), K(+)-ATPase activity showing an additive effect on the sodium pump. Moreover, hydrocortisone reversed URO-DA over-inhibition of the enzyme, confirming that this inhibition is closely related to URO-stimulation on renal DA uptake. URO and DA could act via a common intracellular pathway to decrease sodium and water tubular reabsorption, contributing to its natriuretic and diuretic effects.