Endogenous sodium pump inhibitors, diabetes mellitus and preeclampsia Preliminary observations and a hypothesis.

Endogenous inhibitors of the Na/K-ATPase (NKA) and diabetes mellitus (DM) are both risk factors for preeclampsia and NaCl sensitive hypertension. Our goal was to test the hypothesis that NaCl supplementation, induces preeclampsia-like symptoms in pregnant rats with DM via stimulation of marinobufagenin (MBG), a natriuretic and vasoconstrictor inhibitor of the NKA. Type 2 DM in female Sprague-Dawley rats was induced by administration of 65mg/kg streptozotocin at day 4 post-partum.

Endogenous digitalis-like ligands and Na/K-ATPase inhibition in experimental diabetes mellitus.

Dysregulation of the Na/K-ATPase (NKA) in the kidney, cardiovascular system, and peripheral nervous system is believed to contribute to pathogenesis of diabetes mellitus (DM) and its complications. Recently we demonstrated that, in addition to endogenous ouabain (EO), mammalian tissues contain another NKA inhibitor, a bufadienolide marinobufagenin (MBG). In vitro MBG, a natriuretic and a vasoconstrictor, acts as a selective inhibitor of alpha-1 NKA, the main isoform of the sodium pump in renal tubules and vascular smooth muscle.