title: Early co-expression of cyclooxygenase-2 and renin in the rat kidney cortex contributes to the development of N(G)-nitro-L-arginine methyl ester induced hypertension.
abstract: We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin-angiotensin system in N(G)-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-PGF(1α) (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-PGF(1α) 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.
authors.affiliation: Doctorado en Ciencias Biológicas, Universidad Nacional Autónoma México., Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, México.
authors.forename: Elizabeth Alejandrina
authors.initials: EA
authors.lastname: Guzmán-Hernández
authors.forename: Rafael
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: María Alicia
authors.initials: MA
authors.lastname: Sánchez-Mendoza
authors.forename: Leonardo
authors.initials: L
authors.lastname: Del Valle-Mondragón
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pastelín-Hernández
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ibarra-Barajas
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000803:Angiotensin I / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use; D000068579:Celecoxib / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006977:Hypertension, Renal / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D012083:Renin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D052246:Cyclooxygenase 2 Inhibitors; D010446:Peptide Fragments; D012333:RNA, Messenger; D000804:Angiotensin II; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D000803:Angiotensin I; D002216:Captopril; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D012083:Renin; C118790:angiotensin I (1-7); D000068579:Celecoxib; D019331:NG-Nitroarginine Methyl Ester
keywords: angiotensin (1-7); angiotensin II; angiotensine 1-7; angiotensine II; celecoxib; célécoxib; inhibition de l’oxyde nitrique; nitric oxide inhibition; prostanoids; prostanoïdes