Effects of COX-1 and COX-2 Inhibitors in L- Nitro-L-Arginine Methyl Ester Induced Hypertensive Rats

Abstract

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.

Royal Jelly, A Super Food, Protects Against Celecoxib-Induced Renal Toxicity in Adult Male Albino Rats

“… 41 Progressive functional or structural deterioration in renal tissue throughout a period of months or years is known as CKD 42 , 43 manifested by a < 60 mL/min per 1.73 m 2 reduction in glomerular filtration rate. 44 , 45…”

Celecoxib

“…10 Celecoxib reduces glomerular filtration rate (GFR) and raise blood pressure. 11,12 It causes renal damage, tubular necrosis, dilatation of renal tubules and shrinking of glomeruli. 13 It inhibits gastrointestinal bleeding, ulcers and reduces gastrointestinal effects of NSAIDS.…”