Renal Ca2+ + Mg2+ ATPase in Congestive Heart Failure Due to Diabetes

Abstract

The authors have previously shown that atrial natriuretic peptide (ANP) mediates its cellular effects in part by changes in Ca²⁺ homeostasis in kidney cortex and that Ca²⁺ + Mg²⁺ ATPase is linked to ANP receptors, being reciprocally modulated by the guanylate cyclase system. The present study was designed to examine the status of this coupling in diabetes-induced congestive heart failure and the effect of its alterations on the functional integrity of the renal cell. Ca²⁺ + Mg²⁺ ATPase and guanylate cyclase were tested in hypertensive-diabetic rats (D+H), which develop congestive heart failure (CHF) at ten weeks following streptozotocin (65 mg/kg) injection and abdominal aortic constriction. The ATPase activity was measured by the release of ³²P from [γ-³²P]ATP in the medium. While the guanylate cyclase activity was decreased very rapidly in the hypertensive-diabetic group, the sensitivity of the Ca²⁺ pump to ANP was increased at an early stage (three weeks) and decreased at a late stage (ten weeks) of CHF.

The authors conclude that a defect in coupling between the Ca²⁺ pump and the ANP-receptor system as observed in the D + H group may contribute to the development of nephropathy and CHF.