THE EFFECTS OF HOMOCYSTEINE AND HOMOCYSTEINE-RELATED COMPOUNDS ON CARDIOVASCULAR SYSTEM: ROLE OF GASEOUS TRANSMITTERS NO, H2S AND CO

Objective of this study will be to determine the effects of acute administration of homocysteine and homocysteine-related compounds on rat cardiac muscle and coronary circulation, and the possible contribution of NO, CO and H2S, and oxidative stress in these effects. The research will be conducted in 4 phases: 1) on the preparations of rat right ventricle to determine the effects of DL-homocysteine and DL-homocysteine thiolactone on contractility, and contribution of NO, CO and H2S, using the appropriate inhibitors: for NO (L-NAME, NO synthase inhibitor), for CO (zinc protoporphyrin/ZnPP-IX, inhibitor of heme oxygenase, HO-1) and H2S (DL-propargylglycine, inhibitor of CSE), 2) on the rat left ventricular specimens to determine the effects of DL-homocysteine and DL-homocysteine thiolactone on the oxygen consumption, as well as the contribution of NO, CO and H2S, 3) on the rat myocardium in order to evaluate activity of acetylcholinesterase (AChE), and parameters of oxidative stress in plasma, following the effects of DL-homocysteine and DL-homocysteine thiolactone, or after inhibition of gaseous transmitters synthesis, and 4) on the model of the isolated rat heart according to Langendorff in order to analyze the effects of acute administration of DL-homocysteine and DL-homocysteine thiolactone on coronary flow and the parameters of oxidative stress, as well as after inhibition of gaseous transmitters synthesis.