title: Effects of COX inhibition on blood pressure and kidney function in ACE inhibitor-treated blacks and hispanics.
abstract: Cyclo-oxygenase (COX) inhibitors attenuate the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors and reduce kidney function. The study tests the hypothesis that these two classes of drugs have similar effects on glomerular filtration rate (GFR) and 24-hour blood pressure. The primary endpoint was change in 24-hour systolic blood pressure. Using a randomized crossover design, 25 black and Hispanic hypertensive participants (mean age 58+/-3 years) with osteoarthritis were studied. All participants received an ACE inhibitor at baseline. Once systolic blood pressure was <140 mm Hg, either celecoxib 200 mg/d or diclofenac 75 mg twice daily for 4 weeks was started. After measurements were obtained, all participants underwent a 2-week washout period and crossed over to the other drug for 4 weeks. A significant difference in mean 24-hour systolic blood pressure was noted between groups at 4 weeks (+4.1+/-1.1 mm Hg diclofenac versus +0.6+/-0.6 mm Hg celecoxib; P=0.01). However, because celecoxib has duration of action shorter than 24 hours, we compared ambulatory values at celecoxib trough and peak activities. At peak, no difference in systolic blood pressure was noted between agents (+3.6+/-0.04 mm Hg diclofenac versus +4.2+/-1.9 mm Hg celecoxib; P=0.67). GFR was also differentially affected at 24 hours (-9.9+/-2.4 mL/min diclofenac versus -0.4+/-1.2 mL/min celecoxib; P=0.01). We conclude that diclofenac and celecoxib increase systolic blood pressure at peak levels; however, these agents differ in their 24-hour effects. Differences observed in blood pressure response between COX inhibitors may not be related in their sensitivity but rather their dosing frequency.
authors.affiliation: Rush Medical Center, 1700 W. Van Buren St, Suite 470, Chicago, IL 60612, USA.
authors.forename: Munavvar
authors.initials: M
authors.lastname: Izhar
authors.forename: Tunji
authors.initials: T
authors.lastname: Alausa
authors.forename: Amy
authors.initials: A
authors.lastname: Folker
authors.forename: Elena
authors.initials: E
authors.lastname: Hung
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D000068579:Celecoxib; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004008:Diclofenac / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006630:Hispanic or Latino; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000208:ethnology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy / Q000208:ethnology; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib