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 (losarta n) during treatment for arterial hypertension. In a double-blind crossover design 10 patients with essential arterial hypertension and treated with lo sartan were randomized to supplementary treatment with indomethacin or plac ebo 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 wei ght, peripheral blood now (PBF), and plasma concentrations of aldosterone, renin (PRC), and atrial natriuretic peptide (ANP). Indomethacin did not cha nge BP. Indomethacin increased weight (P <.05) and ECV (P <.05). A nonsigni ficant decrease in UNaV was seen after indomethacin, as in 24-h Cl-Na. Conv ersely in the laboratory in the supine position Cl-Na increased after indom ethacin (P =.05). Indomethacin increased plasma ANP (P <.01). No changes we re observed in GFR, RRI, PBF, PRC, or plasma aldosterone. Thus indomethacin did not attenuate the antihypertensive effect of losartan, neither was per ipheral blood flow affected. Indomethacin caused sodium retention in the no nresting 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 funct ion, when the sympathetic nervous system is activated throughout the day. A m J Hypertens 1999; 12:209-216 (C) 1999 American Journal of Hypertension, L td.