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.

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Administration of L-arginine analogues, such as N-nitro-L-arginine methyl ester (L-NAME) is related with cardiovascular and renal functional alteration. The present experiment was planned to study the possible hemodynamic, renal and liver effects of cyclooxygenase (COX)-1(Aspirin) and COX-2 (Celecoxib) inhibitors in L-NAME induce hypertensive rats. The experimental rats were divided into four groups, each with six animals and the treatments were continued for 2 weeks as the following: Group 1: Control. The rats were given standard rat chow and tap water ad libitum. Group 2: L-NAME. The rats were given standard rat chow and L-NAME (20mg/kg body weight). Group 3: COX-1 inhibitor. The rats were supplied with standard rat chow with aspirin (1000 mg /kg diet) and L-NAME Group 4: COX-2 inhibitor. The rats were supplied with standard rat chow with celecoxib (1000 mg /kg diet) and L-NAME. Results showed that the systolic blood pressure (SBP) was elevated in control rats in comparison with L-NAME group. In the group of receiving COX-1 inhibitor, SBP significantly reduced, while COX-2 inhibitor reduced it but not significantly. Heart rate (H.R) was also changed after COX-2 inhibitor administration ,while COX-1 inhibitor did not change it significantly. COX-1 administration increased serum Na + levels ,while serum K + levels was significantly increased in COX-2 group rats compared with the L-NAME group. Supplementation of L-NAME for 15 days produced a significant increase in serum aspartate transaminase (AST) activity compared with the control group. Statistical analysis revealed that a significant reduction in alanine transaminase (ALT) activity was observed by COX-2 administration compared with the L-NAME. COX-2 inhibitor markedly elevated serum creatinine level compared with the L-NAME group. In conclusions, the results suggested that aspirin rather than celecoxib reduces SBP and in contrast to aspirin, celecoxib alter kidney functions through elevation of serum creatinine level, but it may attenuate liver functions through reduction of elevated serum ALT activity by L-NAME administration.

Ghrelin and leptin are hunger hormones related to type 2 diabetes mellitus (T2DM), and the pathogenesis of T2DM is the abnormality in insulin secretion and insulin resistance (IR). The aim of this study is to evaluate ghrelin and leptin concentrations in blood and to specify the relationship of these hormones as dependent variables with some biochemical and clinical measurements in T2DM patients. In this study, forty one T2DM and forty three non-diabetes mellitus (non-DM) subjects, aged between 40-60 years and with normal weight, were enrolled. Fasting serum ghrelin and leptin were estimated by enzymelinked immunosorbent assay (ELISA). In our results ghrelin was significantly increased, and leptin was significantly decreased, in T2DM patients compared with non-DM subjects. Ghrelin was positively correlated with the fasting blood glucose (FBG) and IR, but inversely related to the insulin sensitivity (IS). Leptin was negatively correlated with mean arterial pressure (MAP), FBG, glycated hemoglobin (HbA1c), IR, low-density lipoprotein cholesterol, nitric oxide (NO), and alanine aminotransferase (ALT), as well as showed a linear correlation with IS and a strong dependence on sex. The area under the curve (AUC) value shows ghrelin and leptin as biomarkers for T2DM. In conclusion ghrelin and leptin hormones have predictive ability to predict T2DM, as they are significantly associated with IR, IS, free radicals, and lipid profile.

The novel finding was that urotensin-II is potentiated under the condition of endothelial dysfunction. Endothelin-1 and angiotensin-II pathways could be heavily exploited in modulating endothelial dysfunction impacts and peptide vascular actions (Tab. 1, Fig. 4, Ref. 30).