The vasodilatory mechanism of nitric oxide and hydrogen sulfide in the human mesenteric artery in patients with colorectal cancer

Abstract

Recent studies have focused on the role of gasotransmitters in cancer progression and prevention. Therefore, the current study was designed to explore the vasodilator activity of NO and H 2 S in the human mesenteric arteries of patients with colorectal cancer (CRC) via the activation of K + channels. A total of two sets of experiments were established for the current investigation. Blood samples from patients with CRC were obtained to detect serum levels of endocan and malondialdehyde (MDA). The role of K + channels in mediating the vasodilation of the human mesenteric artery in response to sodium nitroprusside (SNP) and sodium disulfide (Na 2 S) was assessed. The level of serum endocan was indicated to be decreased in patients with CRC compared with healthy individuals, while the level of serum MDA remained unaltered between groups. The arterial rings pre-contracted with norepinephrine were first relaxed by the cumulative addition of increasing concentrations of either SNP (30 nM-30 µM) or (1-6 mM). Maximal relaxation rates were then calculated at 15 min intervals for 60 min. Pre-incubation of arterial rings for 20 min with individual K + channel blockers was indicated to significantly reduce SNP-and Na 2 S-induced relaxation at different time points. Pre-treatment of L-nitro-arginine methyl ester did not alter vasodilation that was induced by Na 2 S. Furthermore, vasodilation of the CRC mesenteric artery was not altered by the synergistic application of SNP and Na 2 S, while pre-incubation of arterial rings with D,L-propargylglycine significantly enhanced vasodilation induced by SNP. These results indicated that endothelial dysfunction and oxidative stress do not serve roles in the pathogenesis of CRC. The dilatory mechanisms of NO and H 2 S in mesenteric arteries of patients with CRC were K + channel-and time-dependent, and the activity of cystathionine γ-lyase enzyme inhibited the ability of exogenous NO in vasodilation processes.

Roles of H2S and NO in regulating the antioxidant system of Vibrio alginolyticus under norfloxacin stress

“…Many studies focused on the synergistical regulation between the two gases (H 2 S and NO) in smooth muscle, vasodilation in animal, and cobalt toxicity and heat tolerance in plant ( Hosoki, Matsuki & Kimura, 1997 ; Liew et al, 2007 ; Ozfidan-Konakci et al, 2020 ; Hassan, Maulood & Salihi, 2021 ), whereas the research on the synergistic effect of the two gas molecules in regulating the antioxidant system of V. alginolyticus was hardly reported. In fact, the results mentioned above showed that there is significant correlation between the antioxidant system and two gas molecules of H 2 S and NO under the antibiotics stress.…”

Gasotransmitter-Induced Therapeutic Angiogenesis: A Biomaterial Prospective

“…The ischemic tissues of diabetic mice showed reduced phosphorylation of VEGFR, Akt, and ERK proteins and a negative effect on the angiogenic process. When the ischemic limb of diabetic mice was treated with H 2 S, serum levels of VEGF and PDGF were significantly increased with improved wound healing, indicating the involvement of VEGFR signaling in angiogenesis . The H 2 S-mediated VEGF-induced angiogenesis pathway in ischemic limb injury is illustrated in Figure…”

“…Diabetes-induced ischemic injured mice were treated with H 2 S donor sodium bisulfide, and angiogenic transcription factors were quantitated using real-time PCR and Western blotting. Increased expression of VEGF, EGF, PDGF, HIF 1α, and angiogenic factor receptors was observed in the treated animals, indicating the role of H 2 S in angiogenesis-related complications of diabetes . Although studies have shown the positive regulation of H 2 S on diabetes-impaired angiogenesis, the precise regulatory mechanisms are not well understood.…”

“…The exogenous H 2 S increased Akt phosphorylation, while PI3K inhibitors attenuated H 2 S-induced phosphorylation, specifying the role of H 2 S in Akt signaling. The in vivo studies suggested that, when injected intraperitoneally with NaHS, H 2 S showed increased cellular infiltration and new blood vessel formation . The Akt pathway generally induces cell survival by inhibiting the pro-apoptotic factors such as BAD and caspase 9.…”

Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review)

“…Utilizing gasotransmitters as therapeutic aids is justified by their roles in carcinogenesis, including enhancement of apoptotic stimuli, inhibition of metastasis and inhibition of angiogenesis. Therefore, using them alone or in combination with cytotoxic agents is an essential research platform for researchers and clinicians in cancer therapy ( 6 , 140 – 142 ).…”