Effect of Atrial Natriuretic Peptide on Cellular Element Concentrations in Rat Proximal Tubules: Evidence for Inhibition of the Sodium Pump

Abstract

1. In order to further define the action of atrial natriuretic peptide (ANP) on proximal tubular (PT) transport, combined clearance and electron microprobe X-ray (EMPX) experiments were performed on five male Wistar rats infused with ANP (0.16 nmol/kg per h) and nine control animals. 2. Electron microprobe X-ray analysis of PT cell electrolytes (mmol/kg wet weight) revealed a similar [Na]i in both the control and ANP treated groups (16.4 +/- 0.4 vs 16.5 +/- 0.4; P = 0.894). [Cl]i was lower in the ANP treated animals (14.8 +/- 0.3 vs 12.0 +/- 0.3; P < 0.0001) as was [K]i (131.4 +/- 1.4 vs 114 +/- 1.7; P < 0.0001). The PT cells in the ANP treated group had a significant reduction in dry weight (20.1 +/- 0.3 g% vs 19.0 +/- 0.3 g%; P < 0.024), indicating significant cell swelling. Thus, despite a normal [Na]i, there was net accumulation of Nai following ANP treatment. 3. These results are consistent with accumulation of Nai due to inhibition of the Na pump followed by cell swelling and subsequent regulatory volume decrease with exit of K and Cl. These results are the first to show the effect of ANP on PT intracellular electrolytes.

A novel cGMP‐regulated K+ channel in immortalized human kidney epithelial cells (IHKE‐1)

“…However, the cGMP increase in these collecting duct cells is not mediated by natriuretic peptides (Schlatter et al 1996). An inhibitory effect of natriuretic peptides on Na¤-coupled substrate transport in the proximal tubule was postulated previously (Hammond et al 1985;Harris et al 1987;Reddy et al 1994;Eitle et al 1998;Jacobs et al 1999). Besides the possibility of a direct effect of ANP on Na¤-coupled transport proteins, a second possibility would be a decrease in the driving force for Na¤-coupled transport by inhibition of K¤ conductances.…”

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: REGULATION OF RENAL TUBULAR SODIUM TRANSPORT BY ANGIOTENSIN II AND ATRIAL NATRIURETIC FACTOR

“…Reddy et 01. 73 found cell swelling in response to A N F in proximal tubule cells from rat kidneys examined using electron microprobe X-ray analysis and concluded that A N F directly inhibits the sodium pump. A second mechanism involves a cGMP-activated CI-channel found in cultured rat proximal convoluted tubule cells74 that could mediate the action of ANF by allowing CI-to leave the cells and thus reduce the lumen positive driving force for Na* reabsorption.…”