Effects of the angiotensin II antagonist losartan on endothelin-1 and norepinephrine plasma levels during cold pressor test in patients with chronic heart failure

We evaluate the acute hemodynamic and neurohormonal effects of losartan in 15 patients with symptomatic chronic heart failure (CHF), mean age 72+/-8 y ears, which were classified in two subgroups: (A) Patients with left ventri cular ejection fraction (LVEF)less than or equal to 0.35 (n=7); (B) subject s with LVEF>0.35 (n=8). Sympathetic reactivity (blood pressure, heart rate and plasma norepinephrine) and plasma endothelin-1 (ET-1) were evaluated by a cold presser test (CPT). Single doses of losartan (50 mg p.o.) lowered d elta DBP in both subgroups (A, 8+/-9 to 0+/-5 mmHg, P<0.05; B, 10+/-6 to 3/-4 mmHg, P<0.05) and attenuated the rise of HR in patients with mild (4+/- 6 to -1+/-2 bpm, P<0.05) but not with severe (4+/-5 to 2+/-5 bpm, n.s.) imp airment of left ventricular function. Losartan blunted the response (delta) of PNE during CPT (A, 142+/-131 to 10+/-74 pg/ml, P<0.05; B, 129+/-72 to 1 +/-144 pg/ml, P<0.01). A significant rise in plasma ET-1 was observed durin g CPT in patients from subgroup B (0.64+/-0.40 to 0.81+/-0.40 fmol/ml, P<0. 05) but not in patients with LVEF less than or equal to 0.35 (1.79+/-0.44 t o 1.51+/-0.66 fmol/ml, n.s.). Losartan attenuated the rise in ET-1 during C PT in patients with LVEF>0.35 (delta ET-1 0.17+/-0.86 to 0.03+/-0.11 fmol/m l, P<0.05), with no significant changes in subgroup A. Acute effects of los artan were characterized by a more favorable hemodynamic and neurohumoral r esponse in patients with chronic heart failure and preserved systolic ventr icular function related to subjects with lower ejection fractions. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.