title: Effects of the angiotensin II antagonist losartan on endothelin-1 and norepinephrine plasma levels during cold pressor test in patients with chronic heart failure.
abstract: We evaluate the acute hemodynamic and neurohormonal effects of losartan in 15 patients with symptomatic chronic heart failure (CHF), mean age 72+/-8 years, which were classified in two subgroups: (A) Patients with left ventricular ejection fraction (LVEF)< or =0.35 (n = 7); (B) subjects 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 pressor test (CPT). Single doses of losartan (50 mg p.o.) lowered delta DBP in both subgroups (A, 8+/-9 to 0+/-5 mm Hg, P<0.05; B, 10+/-6 to 3+/-4 mm Hg, 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.) impairment 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 during 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< or =0.35 (1.79+/-0.44 to 1.51+/-0.66 fmol/ml, n.s.). Losartan attenuated the rise in ET-1 during CPT in patients with LVEF>0.35 (delta ET-1 0.17+/-0.86 to 0.03+/-0.11 fmol/ml, P<0.05), with no significant changes in subgroup A. Acute effects of losartan were characterized by a more favorable hemodynamic and neurohumoral response in patients with chronic heart failure and preserved systolic ventricular function related to subjects with lower ejection fractions.
authors.affiliation: Services of Internal Medicine, Hospital General La Mancha-Centro, Alcázar de San Juan (Cuidad Real), Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Rodríguez-García
authors.forename: A
authors.initials: A
authors.lastname: Paule
authors.forename: J
authors.initials: J
authors.lastname: Domínguez
authors.forename: J R
authors.initials: JR
authors.lastname: García-Escribano
authors.forename: M
authors.initials: M
authors.lastname: Vázquez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003080:Cold Temperature; D019332:Endothelin-1 / Q000097:blood*; D005080:Exercise Test / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; D000804:Angiotensin II; D019808:Losartan; D009638:Norepinephrine