The vasodilatory mechanism of nitric oxide and hydrogen sulfide in human mesenteric artery of colorectal cancer patients: role of potassium channels

Abstract

Recent studies focused on the role of gasotransmitters in cancer progression and prevention. Therefore, this study was designed to explore the vasodilator activity of NO and H2S in human mesenteric artery of CRC patients via activation of K+ channels. For this purpose, two sets of experiments were established. The blood samples from CRC patients were obtained to detect serum levels of Endocan and MDA. Moreover, the role of K+ channels were assessed in mediating vasodilation of human mesenteric artery in response to SNP and Na2S. The level of serum Endocan was decreased in CRC patients compared to healthy individuals, while serum MDA was not changed. The arterial rings precontracted with NE were first relaxed by cumulative addition of increasing concentrations of either SNP (30nM-30M) or Na2S (1-6mM). Then maximal relaxation rates were calculated for four times at each 15min intervals. Preincubation of arterial rings for 20min with individual K+ channels blockers were significantly reduced relaxation caused by SNP and Na2S at different time intervals. Furthermore, pretreatment of L-NAME did not change the vasodilation induced by Na2S. Vasodilation of CRC mesenteric unchanged by synergistic application of SNP and Na2S. While preincubation of arterial rings with PAG significantly enhanced vasodilation induced by SNP. In conclusion, these results indicate that endothelial dysfunction and oxidative stress do not take part in the pathogenesis of CRC. The dilatory mechanisms of NO and H2S in mesenteric arteries of CRC patients are K+ channels and time dependent, and the activity of CSE enzyme slows down the vasodilator ability of exogenous NO.