Heart 1998;80:134-140 ( August )
Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II
a Clinical
Pharmacology Unit and Research Centre, University of Edinburgh, Western
General Hospital, Crewe Road, Edinburgh, UK, b Cardiovascular Research Unit, University
of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh, UK, c Department of Cardiology, Stobhill Hospital,
Balornock Road, Glasgow, UK
Correspondence to: Dr D E Newby, Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. email: D.E.Newby{at}ed.ac.uk
Accepted for publication 17 March 1998
Objective
To determine
directly the contribution of angiotensin II to basal and
sympathetically stimulated peripheral arteriolar tone in patients with
heart failure.
Design
Parallel group comparison.
Subjects
Nine patients
with New York Heart Association grade II-IV chronic heart failure, and
age and sex matched controls.
Interventions
Forearm
plethysmography, lower body negative pressure, local intra-arterial
administration of losartan, angiotensin II, and noradrenaline, and
estimation of plasma hormone concentrations.
Main outcome
measures
Forearm blood flow responses, plasma
hormone concentrations.
Results
Baseline blood
pressure, heart rate, and forearm blood flow did not differ between
patients and controls. In comparison with the non-infused forearm,
losartan did not affect basal forearm blood flow (95% confidence
interval
5.5% to +7.3%) or sympathetically stimulated
vasoconstriction in controls. However, the mean (SEM) blood flow in
patients increased by 13(5)% and 26(7)% in response to 30 and 90 µg/min of losartan respectively (p < 0.001). Lower body negative
pressure caused a reduction in forearm blood flow of 20(5)% in
controls (p = 0.008) and 13(5)% (p = 0.08) in patients (p = 0.007, controls v patients). Blood
flow at 90 µg/min of losartan correlated with plasma angiotensin II
concentration (r = 0.77; p = 0.03).
Responses to angiotensin II and noradrenaline did not differ between
patients and controls.
Conclusions
Losartan
causes acute local peripheral arteriolar vasodilatation in patients
with heart failure but not in healthy control subjects. Endogenous
angiotensin II directly contributes to basal peripheral arteriolar tone
in patients with heart failure but does not augment sympathetically
stimulated peripheral vascular tone.
© 1998 by Heart
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