Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.

Many of the pathological consequences of chronic kidney disease can be attributed to an elevation in serum phosphate levels. Current therapies focused on decreasing intestinal phosphate absorption to treat hyperphosphatemia are inadequate. The most effective therapeutic strategy may be to target multiple absorptive pathways.

Diabetic cardiomyopathy: the need for adjusting experimental models to meet clinical reality.

Diabetic cardiomyopathy (CM), occurring in the absence of hypertension, coronary artery disease, and valvular or congenital heart disease, is now recognized as a distinct, multifactorial disease leading to ventricular hypertrophy and abnormal myocardial contractility that correlates with an array of complex molecular and cellular changes. Animal models provide the unique opportunity to investigate mechanistic aspects of diabetic CM, but important caveats exist when extrapolating findings obtained from preclinical models of diabetes to humans. Indeed, animal models do not recapitulate the complexity of environmental factors, most notably the duration of the exposure to insulin resistance that may play a crucial role in the development of diabetic CM.

Acute SGLT-2i treatment improves cardiac efficiency during myocardial ischemia independent of Na/H exchanger-1.

Aims: Sodium glucose co-transporter 2 inhibitors (SGLT2i) demonstrate cardioprotective benefits independent of a glucose lowering effect including preservation of cardiac function during a myocardial ischemia. Sodium‑hydrogen exchanger-1 (NHE-1), has been hypothesized to contribute to the cardiac effects of SGLT2i. We characterized the beneficial effects of acute pre-ischemia exposure to SGLT2i and explored the possibility that these effects are explained by NHE-1 inhibition.

Effects of pharmacological inhibition of the sodium-dependent phosphate cotransporter 2b (NPT2b) on intestinal phosphate absorption in mouse and rat models.

An excess phosphate burden in renal disease has pathological consequences for bone, kidney, and heart. Therapies to decrease intestinal phosphate absorption have been used to address the problem, but with limited success. Here, we describe the in vivo effects of a novel potent inhibitor of the intestinal sodium-dependent phosphate cotransporter NPT2b, LY3358966.

Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation.

Regulation of the peripheral vascular resistance via modulating the vessel diameter has been considered as a main determinant of the arterial blood pressure. Phosphodiesterase enzymes (PDE1-11) hydrolyse cyclic nucleotides, which are key players controlling the vessel diameter and, thus, peripheral resistance. Here, we have tested and reported the effects of a novel selective PDE1 inhibitor (BTTQ) on the cardiovascular system.