Early co-expression of cyclooxygenase-2 and renin in the rat kidney cortex contributes to the development of NG-nitro-l-arginine methyl ester induced hypertension

Abstract

We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin–angiotensin system in NG-nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Male Wistar rats were treated with l-NAME (75.0 mg·(kg body mass)−1·day−1, in their drinking water) for different durations (1–33 days). COX-2 and renin mRNA were measured using real-time PCR in the renal cortex, and prostanoids were assessed in the renal perfusate, whereas angiotensin II (Ang II) and Ang (1-7) were quantified in plasma. In some rats, nitric oxide synthase inhibition was carried out in conjunction with oral administration of captopril (30.0 mg·kg−1·day−1) or celecoxib (1.0 mg·kg−1·day−1) for 2 or 19 days. We found a parallel increase in renocortical COX-2 and renin mRNA starting at day 2 of treatment with l-NAME, and both peaked at 19–25 days. In addition, l-NAME increased renal 6-Keto-PGF1α (prostacyclin (PGI2) metabolite) and plasma Ang II from day 2, but reduced plasma Ang (1-7) at day 19. Captopril prevented the increase in blood pressure, which was associated with lower plasma Ang II and increased COX-2-derived 6-Keto-PGF1α at day 2 and plasma Ang (1-7) at day 19. Celecoxib partially prevented the increase in blood pressure; this effect was associated with a reduction in plasma Ang II. These findings indicate that renal COX-2 expression increased in parallel with renin expression, renal PGI2 synthesis, and plasma Ang II in l-NAME-induced hypertension.