Effect of slow-release hydrogen sulfide donor GYY4137 on vascular smooth muscle and endothelial response in an in vitro ischemia-reperfusion model of rat thoracic aorta.

Abstract

Ischemia-reperfusion (IR) injury of vascular grafts used in coronary artery bypass surgery can compromise outcomes. This study examined whether GYY4137, a slow-release hydrogen sulfide donor, protects against IR-induced vascular damage in rat thoracic aorta. Twenty male Sprague-Dawley rats (21-22 months old) were randomly assigned to Control, IR, IR + GYY4137 (100 µM), and IR + GYY4137 (300 µM) groups. To induce IR injury, aortic rings were incubated in nitrogen-gassed saline at 4 °C for 24 h, then exposed to sodium hypochlorite (200 µM) at 37 °C for 30 min. Vascular function was evaluated in organ baths; malondialdehyde, glutathione, and caspase-3 were quantified. IR injury markedly impaired contraction and endothelium-dependent relaxation, which GYY4137 did not restore. In contrast, IR increased malondialdehyde ( = 0.02), which fell to near-control with both 100 µM ( = 0.008) and 300 µM GYY4137 ( = 0.012). IR lowered glutathione ( = 0.012) was restored by 300 µM GYY4137 ( = 0.004). Likewise, caspase-3 rose ( = 0.02) but returned to near-control with both 100 µM ( = 0.004) and 300 µM GYY4137 ( = 0.02). In conclusion, GYY4137 reduces oxidative stress and apoptosis markers without improving vascular dysfunction in an IR model of rat thoracic aorta. This disparity underscores the complex pathophysiology of vascular IR injury, where cellular-level protection does not readily translate to functional recovery.