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Angiotensin II receptor blockade, but not ACE inhibition, reduces nocturnal hypertesion and natriuresis in autonomic failure patients with low renin activity
Author(s) -
Arnold Amy C,
Okamoto Luis E,
Gamboa Alfredo,
Shibao Cyndya A,
Raj Satish R,
Robertson David,
Biaggioni Italo
Publication year - 2013
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.27.1_supplement.654.19
Subject(s) - losartan , medicine , endocrinology , captopril , orthostatic vital signs , plasma renin activity , blood pressure , natriuresis , renin–angiotensin system , supine position , angiotensin ii , placebo , pure autonomic failure , alternative medicine , pathology
At least half of autonomic failure [AF] patients exhibit paradoxic supine hypertension. However, the underlying mechanisms and optimal treatment strategies for this condition are unknown. While renin activity is often undetectable, we recently showed that circulating Ang II levels are elevated in AF patients. Thus, we tested the hypothesis that endogenous Ang II contributes to the hypertension of AF. The AT 1 receptor blocker losartan (50 mg) was administered at bedtime to 11 hypertensive AF patients in a randomized, double‐blind, placebo‐controlled study. Seven AF patients also received the ACE inhibitor captopril. Plasma Ang II was increased in AF patients [52±5 pg/ml] relative to matched healthy subjects [27±4 pg/ml; p=0.002], despite similar low renin activity. Losartan maximally reduced systolic blood pressure by 32±11 mmHg [p<0.05], decreased nocturnal urinary sodium excretion [0.111±0.015 losartan vs 0.151±0.008 mmol/mg placebo, p=0.046] and did not worsen morning orthostatic tolerance [404±163 losartan vs 530±194 mmHg*min placebo, p=0.687]. There was no effect of captopril on supine blood pressure, sodium excretion or orthostatic tolerance in AF perhaps suggesting that the Ang II generation is independent of ACE activity. These findings suggest that elevations in Ang II contribute to the hypertension of AF and provide new rationale for use of AT 1 receptor blockers in treatment of these patients. Support: NIH grants P01 HL‐056693, UL1 TR000445 and AHA 11POST7330010.