title: Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure.
abstract: The aim of this study was to compare the effects on BP and sympathetic activity of chronic treatment with an angiotensin (Ang)-converting enzyme (ACE) inhibitor and an AngII receptor blocker in hypertensive patients with chronic renal failure (CRF). In ten stable hypertensive CRF patients (creatinine clearance, 46 +/- 17 ml/min per 1.73 m(2)), muscle sympathetic nerve activity (MSNA), plasma renin activity (PRA), baroreceptor sensitivity, and 24-h ambulatory BP were measured in the absence of antihypertensive drugs (except diuretics) after 6 wk of enalapril (10 mg orally) and after 6 wk of losartan (100 mg orally). The order of the three phases was randomized. Normovolemia was controlled with diuretics and confirmed with extracellular fluid volume measurements throughout the study. Both enalapril and losartan reduced MSNA (from 33 +/- 10 to 27 +/- 13 and 27 +/- 13 bursts/min, respectively; P < 0.05) and average 24-h BP (from 141 +/- 8/93 +/- 8 to 124 +/- 9/79 +/- 8 and 127 +/- 8/81 +/- 9 mmHg; P < 0.01). PRA was not different during the treatments. The change in BP and the change in MSNA during the treatments were correlated (r = 0.70 and r = 0.63, respectively; both P < 0.05). Baroreceptor sensitivity was not affected by the treatments. This is the first study to compare the effects of ACE inhibition and AngII blockade on MSNA. In hypertensive CRF patients, enalapril and losartan equally reduced BP and MSNA. Differences in modes of action of the two drugs did not result in differences in effects on MSNA, supporting the view that AngII-mediated mechanisms contribute importantly in the pathogenesis of sympathetic hyperactivity in these patients.
authors.affiliation: Department of Nephrology, University Medical Center Utrecht, The Netherlands.
authors.forename: Inge H H T
authors.initials: IH
authors.lastname: Klein
authors.forename: Gerry
authors.initials: G
authors.lastname: Ligtenberg
authors.forename: P Liam
authors.initials: PL
authors.lastname: Oey
authors.forename: Hein A
authors.initials: HA
authors.lastname: Koomans
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D019808:Losartan