The action of angiotensin II on the intracellular sodium content of suspensions of rat proximal tubules.
1. Intracellular sodium levels in isolated suspensions of rat proximal tubles were measured by 23Na NMR spectroscopy and the effect of angiotensin II (AII) on these levels was recorded. 2. AII at 10(-11) M produced an increase in intracellular sodium content of approximately 20% (P < 0.001) from the steady-state level 5 min after the addition of the drug; intracellular sodium content then gradually returned to baseline levels over the subsequent 25 min. 3. Addition of AII at 10(-5) M resulted in a significant 20% decrease (P < 0.01) in the steady-state intracellular sodium level within 5 min. Again the effect was transient and steady-state intracellular sodium levels were re-established after 25 min. 4. Amiloride at 10(-4) M significantly attenuated the action of AII at 10(-11) M (P < 0.0001) and inhibited the transient response to AII at 10(-5) M (P < 0.01). When amiloride alone was added to the tubular suspension, intracellular sodium content decreased significantly by 18-22% (P < 0.001), and addition of both the high and low doses of AII did not have any further effect on intracellular sodium level. 5. The actions of both concentrations of AII were unaffected by an inhibitor of endopeptidase-24.11, phosphoramidon at 10(-6) M, which suggests that the transient action of AII was not due to the breakdown of AII by endopeptidase-24.11. 6. It is well known that AII at high doses inhibits and at low doses stimulates sodium transport across proximal tubular epithelial cells. From the present data it is proposed that AII has a transient biphasic action on intracellular sodium content which may reflect the stimulation of the Na(+)-H+ exchanger.
Wong
P S
PS
Department of Physiology, Medical School, Birmingham, UK.
Johns
E J
EJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000032:analysis / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism; D013696:Temperature
D004232:Diuretics; D006020:Glycopeptides; D011480:Protease Inhibitors; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; C008890:phosphoramidon