title: Differential role of cyclooxygenase-1 and -2 on renal vasoconstriction to α₁-adrenoceptor stimulation in normotensive and hypertensive rats.
abstract: OBJECTIVE
  Hypertension is associated with the impairment of renal cyclooxygenase (COX) activity, which regulates vascular tone, salt and water balance and renin release. We aimed to evaluate the functional role of COX isoforms in kidneys isolated from spontaneously hypertensive rats (SHR) after α1-adrenoceptor (α1-AR) stimulation.
  
  
  METHODS
  Male six-month-old SHR and normotensive Wistar-Kyoto rats (WKY) were used. The kidneys were isolated to measure perfusion pressure and COX-1- or COX-2-derived prostanoids in response to α1-AR activation.
  
  
  RESULTS
  The basal perfusion pressure was higher in SHR kidneys compared with WKY kidneys (95 ± 11 vs. 68 ± 6 mmHg, P<0.05). Phenylephrine induced a greater vasopressor response in SHR kidneys (EC50 of 1.89 ± 0.58 nmol) than WKY kidneys (EC50 of 3.30 ± 0.54 nmol, P<0.05 vs. SHR). COX-1 inhibition decreased the α1-AR-induced vasoconstrictor response in WKY but did not affect SHR response, while COX-2 inhibition diminished the response in SHR. Both basal prostacyclin (PGI2) and thromboxane A2 (TxA2) values were higher in SHR kidney perfusates (P<0.05) and were reduced by COX-1 and COX-2 inhibitors in both strains. Furthermore, phenylephrine increased PGI2 through COX-2 in WKY and through COX-1 in SHR, but the agonist did not significantly modify TxA2 in both strains.
  
  
  CONCLUSIONS
  The data suggest that COX-1 contributes to vasoconstrictor effects in WKY kidneys and that COX-2 has the same effect in SHR kidneys. The results also suggest that basal release of COX-2-derived vasoconstrictor prostanoids is involved in renal vascular hypersensitivity in SHR.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, México.
authors.forename: Estela
authors.initials: E
authors.lastname: D'Abril Ruíz-Leyja
authors.forename: Rafael
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: Juan Javier
authors.initials: JJ
authors.lastname: López-Guerrero
authors.forename: Itzell Alejandrina
authors.initials: IA
authors.lastname: Gallardo-Ortíz
authors.forename: Samuel Enoch
authors.initials: SE
authors.lastname: Estrada-Soto
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ibarra-Barajas
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013928:Thromboxane A2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D016861:Cyclooxygenase Inhibitors; D010656:Phenylephrine; D013928:Thromboxane A2; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: COX-1; COX-2; Renal vascular bed; SHR; α(1)-Adrenoceptors