Hemodynamic and renal effects of indomethacin in losartan-treated hypertensive individuals.
This study was undertaken to examine whether prostaglandin (PG) inhibition with indomethacin interferes with angiotensin II receptor blockade (losartan) during treatment for arterial hypertension. In a double-blind crossover design 10 patients with essential arterial hypertension and treated with losartan were randomized to supplementary treatment with indomethacin or placebo for 1 week, with a 2-week washout period interposed. At the end of each treatment period the following examinations were performed, preceded by 4 days on sodium-fixed diet: 24-h blood pressure (BP), 24-h sodium excretion (UNaV), supine BP, glomerular filtration rate (GFR), renal resistive index (RRI), extracellular fluid volume (ECV), sodium clearance (Cl(Na)), body weight, peripheral blood flow (PBF), and plasma concentrations of aldosterone, renin (PRC), and atrial natriuretic peptide (ANP). Indomethacin did not change BP. Indomethacin increased weight (P < .05) and ECV (P < .05). A nonsignificant decrease in UNaV was seen after indomethacin, as in 24-h Cl(Na). Conversely, in the laboratory in the supine position Cl(Na) increased after indomethacin (P = .05). Indomethacin increased plasma ANP (P < .01). No changes were observed in GFR, RRI, PBF, PRC, or plasma aldosterone. Thus indomethacin did not attenuate the antihypertensive effect of losartan, neither was peripheral blood flow affected. Indomethacin caused sodium retention in the nonresting situation, which was not counterbalanced by the increased Cl(Na) in the resting supine position. The observed changes during prostaglandin (PG) inhibition seem most likely due to lack of PG "protection" of renal function, when the sympathetic nervous system is activated throughout the day.
Olsen
M E
ME
Department of Cardiology Y, Bispebjerg Hospital, Copenhagen, Denmark.
Thomsen
T
T
Hassager
C
C
Ibsen
H
H
Dige-Petersen
H
H
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007213:Indomethacin / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000652:urine; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D012964:Sodium; D019808:Losartan; D007213:Indomethacin