Abstract
Norepinephrine (NE) is widely used to treat cardiac arrest and profound hypotension. A prolonged vasoconstriction of blood vessel could cause ischemia and hypoxia which results in a decrease in intracellular pH. V-ATPases pump protons across the plasma membranes of numerous cell types. V-ATPases-mediated intracellular regulation in the ischemic kidney is incompletely studied; we sought to determine the roles of V-ATPases in mice treated with NE causing vasoconstriction or acetylcholine causing vasodilatation to enable comparison of its relative contributions to the affected mice. Mice were divided into 5 groups. Histology and immunohistochemistry were performed to examine pathologic changes in nephron segments. The expression of V-ATPases B1, B2 subunits were examined by Q-PCR and western blotting correlated with the transcription and translation of V-ATPase. All NE treated mice exhibited pronounced renal tubular degradation. However, the tubular pathologies were reversed by ACh. In immunohistochemical studies, NE treated mice showed a higher density of staining in the collecting ducts. These changes were gradually diminished by the treatment with Ach after NE. In Q-PCR, V-ATPase B1 subunit showed a fair expression in all subsets. Western blotting analysis has shown V-ATPase B1 statistical significance in multiple groups treated by NE alone or ACh post to NE. The overdosage of norepinephrine in clinical treatment is harmful to the kidney by vasoconstriction caused hypoxia and acidosis. Our data demonstrated that acetylcholine as a vasodilating agent could aid the cells recovery from hypoxic condition. V-ATPase plays a role by removing H+ allowing cells to recover from cellular acidosis. These findings also help us understand the pathophysiology of renal tubular disorders.