Activation of proximal tubular Na(+)-H+ exchange by angiotensin II

Abstract

Stimulation of Na(+)-H+ exchange by angiotensin II (ANG II) was characterized in renal proximal tubular cells. Rabbit proximal nephron segments were incubated in the presence or absence of ANG II (5 x 10(-10) M), after which brush-border membrane vesicles (BBMV) were isolated and assayed for Na(+)-H+ antiporter activity using the acridine orange technique. Both the affinity (for sodium) and capacity of the carrier were elevated significantly (P less than 0.05) within 15 min of incubation with ANG II. To determine whether the stimulation of transport capacity involved a change in Na(+)-H+ antiporter density in the luminal membrane, binding of tritiated 5-(N-methyl-N-isobutyl)amiloride ([3H]MIA) was measured in BBMV derived from control and ANG II-treated nephron segments, following maximal stimulation. This demonstrated a significant (P less than 0.05) increase in the maximal specific binding (Bmax) of [3H]MIA binding in the ANG II-treated group compared with control, of a magnitude sufficient to account for the observed change in maximal velocity (Vmax). The data indicate that the Vmax effect is caused by an apparent increase in the number (density) of active Na(+)-H+ carriers present in the luminal membrane. Finally, to test the possibility that the observed kinetic change involves an exocytic mechanism, the effect of colchicine on ANG II-stimulated antiporter activity was examined. The increase in Vmax due to ANG II was blocked by the addition of 0.5 mM colchicine to the incubation medium, whereas colchicine alone had no significant effect on the Vmax of Na(+)-H+ kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin treatment enhances AT1receptor function in OK cells

“…At molecular level, ANG II activates AT 1 receptors coupled with G i proteins and modulates multiple second messenger systems such as lowering of cellular cAMP and activation of phospholipase A2 in proximal tubule epithelial cells (26,39). The modulation of these second messenger levels by ANG II leads to the stimulation of tubular sodium transporters, namely, Na/H exchanger, Na-K-ATPase, and Na/HCO 3 cotransporters, thereby increases tubular sodium reabsorption (7,8,15). Numerous studies suggest that an abnormal AT 1 receptor function, either caused by excessive availability of ANG II or increased AT 1 receptor signaling per se, contributes to the shift in pressure natriuresis and the development of hypertension (9,17,25,28,36,37).…”

Depletion of Tissue Angiotensin-Converting Enzyme Differentially Influences the Intrarenal and Urinary Expression of Angiotensin Peptides

“…7 Intrarenal Ang II also increases vasomotor tone at the afferent and efferent arterioles, which may impact glomerular filtration rate. 8,9 Angiotensin-(1-7) [Ang- (1)(2)(3)(4)(5)(6)(7)] is an alternative peptide product of the RAS that has vasodilatory effects in the kidney that may counterbalance the effects of Ang II on vasomotor tone. 10 The relative concentration of the 2 angiotensin peptides determines vasomotor tone in the kidney and regulates filtration across the glomerulus.…”

Intrarenal Renin-Angiotensin System Contributes to Tubular Acidification Adaptation following Uninephrectomy

“…These findings are coincident with the larger proton fluxes in UNx rats found in the present work. AngII modulates the Na + -H + activity of the PCT [8, 9, 10]. Since all the components of the RAS are present in the proximal tubule [14], an autocrine/paracrine role for local RAS has been postulated [32].…”

“…These results suggest that the renin-angiotensin system (RAS) is involved in the control of renal Na + handling of the remnant kidney [7]. Angiotensin II (AngII) modulates Na + -H + exchange in the proximal tubule cell [8, 9]and the brush border membrane [10]. As we have previously pointed out, the activity of this exchanger is increased after uninephrectomy [4].…”