Control of proximal tubule acidification by the endothelium of the peritubular capillaries

Abstract

Guanosine 3',5'-cyclic monophosphate (cGMP), a nitric oxide mediator, stimulates Na+/H+ exchange in brush-border vesicles of the renal cortex. The aim of the present work was to test whether the endothelium of the peritubular capillaries modulated the rate of proximal luminal acidification through the release of endothelium-derived nitric oxide (EDNO). Perfusion of the tubule lumen with dibutyryl cGMP increased net proton flux (J(H)). Two agents that elicit EDNO production, bradykinin (BK) and carbamylcholine (Cch), increased J(H) when added to the peritubular capillary perfusate. Bradykinin did not affect J(H) when the peritubular capillaries and the lumen were perfused with Na-free solution. Methylene blue (MB) and N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the elevation in J(H) by Cch and also decreased basal J(H). Bradykinin increased cGMP content of isolated proximal convoluted tubules, but only if they were coincubated with endothelial cells. This effect of BK was blocked by L-NAME. The results suggest that the endothelium of the peritubular capillaries affects proximal tubule acidification through changes of cGMP in proximal tubule cells, probably via stimulation of Na+/H+ exchanger.

Regulation of an inwardly rectifying K+channel by nitric oxide in cultured human proximal tubule cells

“…In previous reports, some investigators demonstrated the stimulatory effect of NO on the proximal tubular fluid and Na ϩ transport (3,33,34), whereas others showed the inhibitory effect (10,20,32). The diversity of NO action on the proximal tubular cell might partly be caused by the biphasic action of NO (19,22).…”

“…A study using microperfused rat proximal tubules revealed that an NOS inhibitor suppressed the absorption of Na ϩ and HCO 3 Ϫ , whereas NO donors stimulated it, probably by affecting the apical Na ϩ /H ϩ exchange (33). Furthermore, NOS knockout mice exhibited a defect in the proximal tubular absorption of fluid and HCO 3 Ϫ (34).…”

Renal Interstitial cGMP Mediates Natriuresis by Direct Tubule Mechanism

“…Indeed, controversy exists about whether NO stimulates or inhibits sodium transport in specific nephron segments. 16 -20 Although several studies indicate that NO inhibits sodium reabsorption, 16,17,20 others have suggested that NO and cGMP stimulate proton flux and sodium and bicarbonate transport in proximal tubule cells 18,19 and that inhibition of NOS increases fractional sodium excretion. 18 The present study was designed to clarify the role of local generation of cGMP in the renal interstitial space in the control of renal sodium excretion.…”

Decreased NHE8 isoform expression and defective acidification in proximal convoluted tubules of senile rats

“…The Na + /H + exchanger localised in the apical membrane of the proximal tubule is regulated by many factors including, among others, RAS (Reilly et al 1995;Saccomani et al 1990), NO⋅ (Amorena and Castro 1997;Manning et al 1997;Wang 1997), andPTH (Bank andAynedjain 1976).…”

“…The control of proximal acidification is very complex and depends on many factors including, among others, RAS (Reilly et al 1995), NO (Amorena and Castro 1997;Manning et al 1997;Wang 1997), and parathyroid hormone (PTH) (Bank and Aynedjain 1976). The serum concentration of PTH increases with aging in both humans and rats (Fox 1991;Halloran et al 1996).…”