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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/F1336    most recent 00574.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cherney, D. Z. I. Articles by Miller, J. A. PubMed PubMed Citation Articles by Cherney, D. Z. I. Articles by Miller, J. A.

Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus

¹Division of Nephrology, Toronto General Hospital, Divisions of ³Endocrinology and ⁴Cardiology, Hospital for Sick Children, University of Toronto, Toronto; and ²Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

Submitted 20 November 2007 ; accepted in final form 1 April 2008

In experimental studies, cyclooxygenase 2 (COX2)-derived vasodilatory prostaglandins play a more prominent role in arterial vasoregulation in females. The gender-dependent effect of COX2 modulation in humans with type 1 diabetes mellitus (DM) is unknown. Accordingly, we examined the renal hemodynamic role of prostaglandins by assessing the response to COX2 inhibition in young men and women with type 1 DM. We also used a graded ANG II infusion to determine whether gender-based differences were mediated by effects of COX2 inhibition on the renin angiotensin system (RAS). We hypothesized that COX2 inhibition would be associated with preferential vasoconstriction in women and would augment their response to ANG II. Baseline renal function and the response to an ANG II infusion were assessed during clamped euglycemia, and again after COX2 inhibition (200 mg celecoxib daily for 14 days) in 12 men and 9 women after 1 wk on a controlled protein and sodium diet. COX2 inhibition was associated with increases in filtration fraction (P = 0.045) and renal vascular resistance and a decline in renal blood flow (P = 0.04) in women compared with men. Before COX2 inhibition, women exhibited a decline in glomerular filtration rate in response to ANG II. COX2 inhibition abolished this effect, whereas the response was not altered in men. In summary, COX2 inhibition was associated with hemodynamic effects that differed based on gender. The ANG II response suggests that with uncomplicated type 1 DM, prostaglandins may contribute to RAS-mediated gender differences. Our results are consistent with experimental data suggesting augmented female prostanoid dependence.

gender; cyclooxygenase 2 inhibition; type 1 diabetes mellitus; glomerular filtration rate; angiotensin II