26Recent studies focused on the role of gasotransmitters in cancer 27 progression and prevention. Therefore, this study was designed to explore 28 the vasodilator activity of NO and H 2 S in human mesenteric artery of CRC 29 patients via activation of K + channels. For this purpose, two sets of 30 experiments were established. The blood samples from CRC patients were 31 obtained to detect serum levels of Endocan and MDA. Moreover, the role of 32 K + channels were assessed in mediating vasodilation of human mesenteric 33 artery in response to SNP and Na 2 S. The level of serum Endocan was 34 decreased in CRC patients compared to healthy individuals, while serum 35 MDA was not changed. The arterial rings precontracted with NE were first 36 relaxed by cumulative addition of increasing concentrations of either SNP 37 (30nM-30μM) or Na 2 S (1-6mM). Then maximal relaxation rates were 38 calculated for four times at each 15min intervals. Preincubation of arterial 39 rings for 20min with individual K + channels blockers were significantly 40 reduced relaxation caused by SNP and Na 2 S at different time intervals. 41 Furthermore, pretreatment of L-NAME did not change the vasodilation 42 induced by Na 2 S. Vasodilation of CRC mesenteric unchanged by synergistic 43 application of SNP and Na 2 S. While preincubation of arterial rings with PAG 44 significantly enhanced vasodilation induced by SNP. In conclusion, these 45 results indicate that endothelial dysfunction and oxidative stress do not take 46 part in the pathogenesis of CRC. The dilatory mechanisms of NO and H 2 S 47 3 48 and the activity of CSE enzyme slows down the vasodilator ability of 49 exogenous NO. 50 Introduction 53 Colorectal cancer (CRC) is the third most frequently occurring 54 malignancy and the second leading mortality cause of cancer worldwide. 55 More than 1.8 million new CRC cases and 881,000 deaths was reported in 56 2018, accounting for about 1 in 10 cases and deaths [1]. Regardless of, the 57 low incidence of CRC in the Middle East [2], the Kurdistan region of Iraq 58 has a higher annual incidence rate of cancer, and it represents about 38 to 59 61.7 cases/100,000 population and it's the fourth cancer in both sexes 60 separately, and the cause of mortality of about 8.6% [3]. The most common 61 histopathological type of CRC in this region is adenocarcinoma [4]. 62 Endogenous gasotransmitters mainly nitric oxide (NO), carbon 63 monoxide (CO), and hydrogen sulfide (H 2 S) are generated endogenously by 64 specific enzymes [5]. NO is produced from L-arginine by the enzyme NO 65 synthase (NOS) [6, 7] while H 2 S is synthesised from L-cysteine by either 66 cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) or 67 mercaptopyruvate sulfurtransferase (MST) [8, 9]. They can modulate 68 different biological pathways and functions at a physiologically relevant 69 concentration [10] by the opening of various kinds of membrane ion 4 70 channels [11]. NO is an essential regulator of angiogenesis [12] and 71 vasorelaxation through activation of gua...