title: Renal nerve stimulation leads to the activation of the Na+/H+ exchanger isoform 3 via angiotensin II type I receptor.
abstract: Renal nerve stimulation at a low frequency (below 2 Hz) causes water and sodium reabsorption via α1-adrenoreceptor tubular activation, a process independent of changes in systemic blood pressure, renal blood flow, or glomerular filtration rate. However, the underlying mechanism of the reabsorption of sodium is not fully understood. Since the sympathetic nervous system and intrarenal ANG II appear to act synergistically to mediate the process of sodium reabsorption, we hypothesized that low-frequency acute electrical stimulation of the renal nerve (ESRN) activates NHE3-mediated sodium reabsorption via ANG II AT1 receptor activation in Wistar rats. We found that ESRN significantly increased urinary angiotensinogen excretion and renal cortical ANG II content, but not the circulating angiotensinogen levels, and also decreased urinary flow and pH and sodium excretion via mechanisms independent of alterations in creatinine clearance. Urinary cAMP excretion was reduced, as was renal cortical PKA activity. ESRN significantly increased NHE3 activity and abundance in the apical microvillar domain of the proximal tubule, decreased the ratio of phosphorylated NHE3 at serine 552/total NHE3, but did not alter total cortical NHE3 abundance. All responses mediated by ESRN were completely abolished by a losartan-mediated AT1 receptor blockade. Taken together, our results demonstrate that higher NHE3-mediated proximal tubular sodium reabsorption induced by ESRN occurs via intrarenal renin angiotensin system activation and triggering of the AT1 receptor/inhibitory G-protein signaling pathway, which leads to inhibition of cAMP formation and reduction of PKA activity.
authors: Departamento de Fisiologia, Disciplina de Fisiologia Cardiovascular, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors: Roberto B
authors: RB
authors: Pontes
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Renato O
authors: RO
authors: Crajoinas
authors: Departamento de Fisiologia, Disciplina de Fisiologia Cardiovascular, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors: Erika E
authors: EE
authors: Nishi
authors: Departamento de Fisiologia, Disciplina de Fisiologia Cardiovascular, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors: Elizabeth B
authors: EB
authors: Oliveira-Sales
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Adriana C
authors: AC
authors: Girardi
authors: Departamento de Fisiologia, Disciplina de Fisiologia Cardiovascular, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors: Ruy R
authors: RR
authors: Campos
authors: Departamento de Fisiologia, Disciplina de Fisiologia Cardiovascular, Universidade Federal de São Paulo, São Paulo, Brazil; and bergamaschi.cassia@unifesp.br.
authors: Cássia T
authors: CT
authors: Bergamaschi
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D009318:Natriuresis; D010766:Phosphorylation; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D065608:Renal Reabsorption / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013997:Time Factors; D014563:Urodynamics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000808:Angiotensinogen; D000804:Angiotensin II; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: ANG II; AT1 receptor and NHE3; sympathetic nervous system