{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:17:51Z","timestamp":1778275071534,"version":"3.51.4"},"reference-count":28,"publisher":"Portland Press Ltd.","issue":"9","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:p>In patients with CHF (chronic heart failure) sympathetic activity increases as cardiac performance decreases and filling pressures increase. We hypothesized that in patients with mild-to-moderate CHF, higher than conventional doses of an AT1-receptor [AngII (angiotensin II) type\u00a01 receptor] antagonist would achieve greater central AT1-receptor blockade, resulting in diminished MSNA (muscle sympathetic nerve activity) and augmented MSNA variability, two indices of central effects on sympathetic outflow. In total, 13 patients with ischaemic cardiomyopathy [NYHA (New York Heart Association) class II\u2013III] were weaned off all pharmacological RAS (renin\u2013angiotensin system) modifiers, and then randomized to receive a low (50\u00a0mg\/day) or high (200\u00a0mg\/day) dose of losartan. Central haemodynamics, MSNA and its variability, plasma catecholamines, AngI (angiotensin I) and AngII and aldosterone were assessed both before and 3 months after randomization. Neither dose altered BP (blood pressure), PCWP (pulmonary capillary wedge pressure) or CI (cardiac index) significantly. Compared with 50\u00a0mg daily, losartan 200\u00a0mg\/day decreased MSNA significantly (P&amp;lt;0.05), by approximately 15 bursts\/min, and increased MSNA variability within the 0.27\u20130.33 Hz high-frequency range by 0.11 units2\/Hz (P=0.06). PNE [plasma noradrenaline (norepinephrine)] fell in parallel with changes in MSNA (r=0.62; P&amp;lt;0.05). These findings support the hypothesis that higher than conventional doses of lipophilic ARBs (AT1-receptor blockers) can modulate the intensity and variability of central sympathetic outflow in patients with CHF. The efficacy and safety of this conceptual change in the therapeutic approach to heart failure merits prospective testing in clinical trials.<\/jats:p>","DOI":"10.1042\/cs20120437","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T12:42:57Z","timestamp":1353415377000},"page":"589-595","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Do high doses of AT1-receptor blockers attenuate central sympathetic outflow in humans with chronic heart failure?"],"prefix":"10.1042","volume":"124","author":[{"given":"Marcel","family":"Ruzicka","sequence":"first","affiliation":[{"name":"Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada"},{"name":"Division of Nephrology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John\u00a0S.","family":"Floras","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew\u00a0J. 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