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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.

Urotensin-II (UII), a pluripotent vasoactive cyclic peptide, exhibits the progression of cardiovascular diseases and the glucose metabolic disorder of insulin resistance. Type 2 Diabetes Mellitus (T2DM) is entirely associated with insulin resistance. This study aimed to demonstrate the association of UII with insulin resistance in diabetic and non-diabetic subjects. A total of 73 male and female subjects aged 40-60 years were recruited in this case-control study. They included 35 non- diabetic subjects with a body mass index of (BMI) ≤ 25 and 38 patients with Diabetes Mellitus and BMI ≥ 25. UII levels were assessed beside other vasoactive and clinical parameters.     The results revealed that patients with T2DM had elevated UII and Endothelin-I (ET-I) levels, along with positive correlations with the insulin-resistance marker of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), blood pressure (BP), fasting blood glucose (FBG), hemoglobin A1c (HbA1C), and asymmetric dimethylarginine (ADMA). Results from stepwise multiple regressions indicated that UII correlated positively with the increases in the levels of serum cholesterol, ET-I, urea, ADMA, and FBG. This study concludes that the increase in UII level has a positive relation with insulin-resistance and the increase in ET-I level. However, UII could inhibit glucose-induced insulin secretion and, hence, can be utilized as a marker for T2DM and its complications through inflammatory microangiopathy.

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Endothelin-I (ET-I) is one of the potent vasoconstrictors secreted from endothelial cells when needed. Many studies revealed the elevation of serum ET-I with human diabetes and microangiopathies. Since insulin resistance is a case of mixed diabetic and pre-diabetic cases, many risk factors beyond obesity and inflammation are proposed. The current study aims to demonstrate the association between serum ET-I and asymmetric dimethylarginine (ADMA) and insulin resistance in type 2 diabetes mellitus (T2DM). Sera of 73 subjects were enrolled currently (control= 35 subjects, and 38 with T2DM for more than 7 years), aged (40-60) years old, with distinct body mass index (BMI) ≤ 25 for control volunteers and (BMI) ≥ 25 for obesity and diabetes patients. Peripheral serum ET-I and ADMA levels were significantly (P≤ 0.0001) higher in T2DM than the control subjects. Receiver operating characteristic curve analysis regarded ET-I and ADMA as good markers for T2DM disease and insulin resistance, correlations between ET-I and anthropometrics revealed a strong increase of urotensin-II (UII), ADMA, homeostatic model assessment for insulin resistance (HOMA-IR) and hemoglobin A1C (HbA1C) with an increase of ET-I. These results are supported by the data of multiple regression analysis, showing that HOMA-IR, HbA1C, UII, BMI, and mean arterial pressure (MAP) are related to ET-I independently. The endothelin-I and ADMA had a positive relationship with increase insulin resistance and may serve as prognostic and diagnostic clinical biomarkers of insulin resistance. Collectively, Therefore, these measurements could evaluate the incidence of DM, and help to better rise up the knowledge about the progression of DM complications.