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Angiotensin II, independent of plasma renin activity, contributes to the hypertension of autonomic failure.

Hypertension (Dallas, Tex. : 1979) (2012-12-26)
Amy C Arnold, Luis E Okamoto, Alfredo Gamboa, Cyndya Shibao, Satish R Raj, David Robertson, Italo Biaggioni
ABSTRACT

At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. Although the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable, suggesting renin-angiotensin (Ang) pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that Ang II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating Ang II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/mL, n=11) compared with matched healthy controls (27±4 pg/mL, n=10; P=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/mL per hour, respectively; P=0.449). To determine the contribution of Ang II to supine hypertension in these patients, we administered the AT(1) receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mm Hg at 6 hours after administration (P<0.05), decreased nocturnal urinary sodium excretion (P=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of captopril on supine blood pressure in a subset of these patients. These findings suggest that Ang II formation in autonomic failure is independent of plasma renin activity, and perhaps Ang-converting enzyme. Furthermore, these studies suggest that elevations in Ang II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT(1) receptor blockers for treatment of these patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Captopril, meets USP testing specifications
Sigma-Aldrich
Captopril, ≥98% (HPLC), powder
Supelco
Captopril, Pharmaceutical Secondary Standard; Certified Reference Material