title: Haemodynamic and renal responses to oral losartan potassium during salt depletion or salt repletion in normal human volunteers.
abstract: We examined the haemodynamic and renal response to oral losartan potassium (100 mg) during activation of the renin system in humans. Eight healthy volunteers followed a low-salt (40 mmol sodium) diet for 4 days on four occasions 2 weeks apart. Double-blind salt depletion was achieved by 3-day administration of frusemide (40 mg twice daily, b.i.d.) with placebo salt replacement, salt repletion by placebo frusemide (b.i.d.), and active salt replacement (100 mmol/day). On day 4, subjects received randomised double-blind placebo or losartan. Prestudy salt depletion was associated with nonsignificant decreases in serum sodium (138 +/- 2 mM), potassium (3.5 +/- 0.2 mM) and increased urea (6.5 +/- 1.1 mM), and creatinine (91 +/- 6 microM) as compared with screening. Prestudy (day 3) 24-h urinary volume was similar during deplete preparation (placebo 1.707 +/- 0.81 L, losartan 1.509 +/- 0.626 L) or deplete preparation (placebo 1.726 +/- 0.5 L, losartan 1.764 +/- 0.52 L), but sodium excretion was greater during replete preparation. Salt replete supine blood pressure (BP) profiles showed little effect of losartan (mean maximal supine BP -9 +/- 6 mm Hg) as compared with placebo (-1 +/- 4 mm Hg), with a similar relative result for erect BP. After salt depletion, losartan caused a greater response in both supine (-24 +/- 9) and erect (-33 +/- 15) BP than did placebo (supine -12 +/- 5, erect -14 +/- 9). In this protocol after salt depletion, losartan caused a transient increase in urea and creatinine (143 +/- 40 microML) 8 h after dosing as compared with placebo (105 +/- 13 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
authors.forename: J K
authors.initials: JK
authors.lastname: Doig
authors.forename: R J
authors.initials: RJ
authors.lastname: MacFadyen
authors.forename: C S
authors.initials: CS
authors.lastname: Sweet
authors.forename: J L
authors.initials: JL
authors.lastname: Reid
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000652:urine; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004573:Electrolytes / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D019808:Losartan; D008297:Male; D012083:Renin / Q000097:blood; D012964:Sodium / Q000172:deficiency* / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004573:Electrolytes; D007093:Imidazoles; D013777:Tetrazoles; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D003404:Creatinine; D012083:Renin; D019808:Losartan