Differential role of cyclooxygenase-1 and -2 on renal vasoconstriction to a1-adrenoceptor stimulation in normotensive and hypertensive rats
Por:
Ruiz-Leyja, ED, Villalobos-Molina R., López-Guerrero J.J., Gallardo-Ortíz I.A., Estrada-Soto S.E., Ibarra-Barajas M.
Publicada:
11 oct 2013
Resumen:
Aims 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 a1- adrenoceptor (a1-AR) stimulation. Main 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 a1-AR activation. Key findings The basal perfusion pressure was higher in SHR kidneys compared with WKY kidneys (95 ± 11 vs. 68 ± 6 mm Hg, 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 a1-AR-induced vasoconstrictor response in WKY but did not affect SHR response, while COX-2 inhibition diminished the response in SHR. Both basal prostacyclin (PGI 2) 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. Significance The data suggest that COX-1contributes 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. © 2013 Elsevier Inc.
Filiaciones:
Ruiz-Leyja, ED:
Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Los Reyes Iztacala 54090, Tlalnepantla, Mexico
Villalobos-Molina R.:
Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Los Reyes Iztacala 54090, Tlalnepantla, Mexico
López-Guerrero J.J.:
Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Los Reyes Iztacala 54090, Tlalnepantla, Mexico
Gallardo-Ortíz I.A.:
Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Los Reyes Iztacala 54090, Tlalnepantla, Mexico
Estrada-Soto S.E.:
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico
Ibarra-Barajas M.:
Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Los Reyes Iztacala 54090, Tlalnepantla, Mexico
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