Angiotensin regulates the selectivity of the Na+-K+ pump for intracellular Na+

Treatment of rabbits with angiotensin-converting enzyme (ACE) inhibitors increases the apparent affinity of the Na⁺-K⁺ pump for Na⁺. To explore the mechanism, we voltage clamped myocytes from control rabbits and rabbits treated with captopril with patch pipettes containing 10 mM Na⁺. When pipette solutions were K⁺ free, pump current (I(p)) for myocytes from captopril-treated rabbits was nearly identical to that for myocytes from controls. However, treatment caused a significant increase in I(p) measured with pipettes containing K⁺. A similar difference was observed when myocytes from rabbits treated with the ANG II receptor antagonist losartan and myocytes from controls were compared. Treatment-induced differences in I(p) were eliminated by in vitro exposure to ANG II or phorbol 12-myristate 13- acetate or inclusion of the protein kinase C fragment composed of amino acids 530-558 in pipette solutions. Treatment with captopril had no effect on the voltage dependence of I(p). We conclude that ANG II regulates the pump's selectivity for intracellular Na⁺ at sites near the cytoplasmic surface. Protein kinase C is implicated in the messenger cascade.