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(Hypertension. 2004;44:230.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

Jorge A. Rodriguez; Carlos P. Vio; Paulina L. Pedraza; John C. McGiff; Nicholas R. Ferreri

From the Department of Physiology (J.A.R., C.P.V.), Pontificia Universidad Catolica de Chile, Santiago, Chile; and the Department of Pharmacology (P.L.P., J.C.M., N.R.F.), New York Medical College, Valhalla.

Correspondence to Carlos P. Vio, MD, Departamento de Ciencias Fisiologicas, Pontificia Universidad Catolica de Chile, Alameda 340, Santiago, Chile. E-mail cvio{at}bio.puc.cl

Cyclooxygenase-2 (COX-2) is constitutively expressed in a subset of thick ascending limb cells in the cortex and medulla and increases when the renin-angiotensin and kallikrein-kinin systems are activated. Although the contribution of angiotensin II to the regulation of COX-2 is known, the effects of bradykinin on COX-2 expression have not been determined in this nephron segment. We evaluated expression of B2 bradykinin receptors in thick ascending limb cells containing COX-2 and the effect of bradykinin on COX-2 expression in primary cultured medullary thick ascending cells. The presence of B2 receptors was studied in renal sections by immunohistochemistry with antibodies against B2, COX-2, and Tamm-Horsfall glycoprotein. B2 receptors were detected on the apical and basolateral portion of the thick ascending cells. These cells also contained COX-2, suggesting that COX-2 expression may be regulated via B2 receptor. Incubation of cultured medullary thick ascending cells with bradykinin (10^–7 to 10^–5 mol/L) induced a significant increase on COX-2 protein expression. Maximal expression of COX-2 was observed 4 hours after exposure to bradykinin (10^–7 mol/L), effect abolished by a B2 receptor antagonist (HOE-140; 10^–6 mol/L). Prostaglandin E₂ production increased when these cells were challenged with bradykinin for 4 hours, indicating that COX-2 was enzymatically active. We have demonstrated (1) the presence of B2 receptors in thick ascending limb cells expressing COX-2 and (2) the stimulatory effect of bradykinin on COX-2 protein expression, via B2 receptors, in cultured medullary thick ascending cells. We suggest that bradykinin can affect ion transport in the thick ascending limb via a COX-2–mediated mechanism.

Key Words: cyclooxygenase • bradykinin • immunohistochemistry • rats • kidney • receptors, bradykinin • prostaglandins

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