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Angiotensin II contributes to sympathetically‐mediated hypertension in autonomic failure (875.4)
Author(s) -
Arnold Amy,
Okamoto Luis,
Gamboa Alfredo,
Shibao Cyndya,
Raj Satish,
Robertson David,
Biaggioni Italo
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.875.4
Subject(s) - losartan , medicine , angiotensin ii , supine position , angiotensin ii receptor type 1 , blood pressure , sympathetic nervous system , endocrinology , peripheral , cardiology
Angiotensin (Ang) II contributes to hypertension by direct vasoconstriction, and indirectly by promoting sympathetic activation. The importance of the latter to blood pressure regulation remains controversial, particularly in clinical populations. As a novel approach to test the hypothesis that Ang II promotes sympathetically‐mediated hypertension, we compared depressor responses to the Ang II AT1 receptor antagonist losartan in central autonomic failure (AF) patients in whom supine hypertension is driven by residual sympathetic tone to peripheral AF patients with noradrenergic denervation and sympathetic‐independent hypertension. Single dose losartan (50 mg, PO) was administered at bedtime to 10 peripheral and 7 central AF patients, with supine blood pressure measured q2 hours for 12 hours in a randomized, double‐blind, placebo‐controlled study. There were no differences in plasma Ang II levels between groups (42±3 central vs. 43±5 pg/ml peripheral AF; p=0.734); however, peak depressor responses to losartan were significantly greater in central (‐43±10 mmHg) compared to peripheral AF patients (‐19±8 mmHg; p<0.05). These findings suggest that Ang II contributes to residual sympathetic tone in central autonomic failure, and through this mechanism to hypertension. Overall, these patients provide a unique model to assess the importance of Ang II‐sympathetic interactions in human hypertension. Grant Funding Source : Supported by AHA grant 11POST7330010 and NIH grants HL056693, 5U54NS065736 and UL1TR000445.