Valsartan improves mitochondrial function in hearts submitted to acute ischemia.
The effect of valsartan, an angiotensin II-type I receptor blocker, on the mitochondrial function, was studied using an ex vivo animal model (hearts from Wistar rats), perfused in a Langendorff system and then submitted to global acute ischemia. Parameters evaluated were: membrane electrical potential (DeltaPsi, using a tetraphenylphosphonium-TPP+-electrode), oxygen consumption by the respiratory chain (Clark-type O2 electrode), phosphorylation lag phase (time necessary to phosphorylate a fixed amount of ADP) and ATP/ADP ratio (adenine nucleotides quantified by high-pressure liquid chromatography-HPLC). Valsartan acts preferentially in the phosphorylation, increasing ATP/ADP ratios (succinate: 1.6+/-0.4 versus 0.5+/-0.1--P<0.05; ascorbate/N,N,N',N'-tetramethyl-P-phenylenodiamine-TMPD: 1.1+/-0.2 versus 0.4+/-0.1--p<0.05 versus ischemia in the absence of valsartan) and decreasing lag phase (glutamate/malate: 50.0+/-9.6 s versus 127.2+/-19.03 s-84.6+/-16.2% versus 215.3+/-32.2%; P=0.01; succinate: 111.8+/-33.1 s versus 275.73+/-45.99 s-168.2+/-49.8% versus 414.9+/-69.2%; P=0.02 or ascorbate/TMPD: 11.0+/-3.9 s versus 62.4+/-11.63 s-34.9+/-12.4% versus 198.1+/-36.9%; P=0.001 versus ischemia in the absence of valsartan). This enables a higher energy production in hearts submitted to acute ischemia, for which having energy becomes critical to preserve mitochondrial function. These mechanisms allow us to better understand valsartan cytoprotection in ischemic cardiomyopathy.
Monteiro
Pedro
P
Basic Research Unit in Cardiology, Cardiology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal.
Duarte
Ana I
AI
Gonçalves
Lino M
LM
Providência
Luís A
LA
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000244:Adenosine Diphosphate; D000068756:Valsartan; D000255:Adenosine Triphosphate; D014633:Valine