bgp-15 and Hypertension

Heart failure (HF) is a complex chronic clinical disease characterized by among others the damage of the mitochondrial network. The disruption of the mitochondrial quality control and the imbalance in fusion-fission processes lead to a lack of energy supply and, finally, to cell death. BGP-15 (O-[3-piperidino-2-hydroxy-1-propyl]-nicotinic acid amidoxime dihydrochloride) is an insulin sensitizer molecule and has a cytoprotective effect in a wide variety of experimental models. In our recent work, we aimed to clarify the mitochondrial protective effects of BGP-15 in a hypertension-induced heart failure model and "in vitro." Spontaneously hypertensive rats (SHRs) received BGP-15 or placebo for 18 weeks. BGP-15 treatment preserved the normal mitochondrial ultrastructure and enhanced the mitochondrial fusion. Neonatal rat cardiomyocytes (NRCMs) were stressed by hydrogen-peroxide. BGP-15 treatment inhibited the mitochondrial fission processes, promoted mitochondrial fusion, maintained the integrity of the mitochondrial genome, and moreover enhanced the de novo biogenesis of the mitochondria. As a result of these effects, BGP-15 treatment also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure during hydrogen peroxide-induced oxidative stress as well as in an "in vivo" heart failure model. It offers the possibility, which pharmacological modulation of mitochondrial quality control under oxidative stress could be a novel therapeutic approach in heart failure.

Topics: Animals; Animals, Newborn; Cell Culture Techniques; Citrate (si)-Synthase; DNA; DNA Damage; DNA, Mitochondrial; Dynamins; Electron Transport; Energy Metabolism; Genome, Mitochondrial; Heart Failure; Hypertension; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Dynamics; Mitochondrial Proteins; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Organelle Biogenesis; Oxidative Stress; Oximes; Oxygen Consumption; Piperidines; Rats, Inbred SHR; Rats, Inbred WKY