P45 Hydrogen sulfide protects coronary artery vasospasm after myocardial infarction and eliminates myocardial infarction zone by promoting to growth new vessels

Abstract

Hydrogen sulfide (H 2 S) has recently been identified as a regulator of various physiological events including vasodilation, angiogenesis, antiapoptotic, and cellular signaling. H 2 S leads to down-regulation of inflammatory responses and provides myocardial protection during acute myocardial infarction (MI). We previously reported that H 2 S inhibits antiangiogenic factors such as endostatin and angiostatin, leading to development of new vessels. We have shown that coronary vessels elicited vasoconstriction to acetylcholine (Ach) and revealed a phenomenon of vasospasm; we examined the role of hyperhomocysteinemia in coronary endothelial dysfunction, vessel wall thickness, and lumen narrowing, which leads to acute/chronic coronary vasospasm. We hypothesize that H 2 S eliminates vessel damage and improves endothelial function, which causes the elimination of coronary vaso-constriction. To verify this, MI was created in wild-type mice, which were treated with sodium hydrosulfide (NaHS, H 2 S donor) in drinking water and compared with untreated control mice. The echocardiography in mice treated with H 2 S showed improvement of heart function compared to untreated mice. The X-ray and Doppler blood flow measurements showed enhancement of cardiac-angiogenesis in mice treated with H 2 S. This observed cardio-protection was associated with an inhibition of anti-angiogenic proteins and stimulation of angiogenic factors. The endothelium-impaired arteries from MI mice were constricted in response to Ach, and this vasoconstriction was mitigated with NaHS supplementation. The level of endothelial nitric oxide synthase (eNOS) was lower in coronary artery in MI than of MI + NaHS mice. Treatment with NaHS increased the levels of Ach-induced NO generation in the coronary artery of MI mice. The results suggest that Ach induced coronary vasoconstriction in MI mice and this vasoconstriction was ameliorated by NaHS treatment. The mechanisms for the impairment of vascular function and therapeutic effects of NaHS may be related to the regulation of eNOS expression, NO availability and tissue homocysteine. We established that administration of NaHS at the time of MI ameliorated infarct size and preserved LV function during development of MI in mice, which also improved coronary endothelial function and promoted new vessel growth.