Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II
- aClinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, UK, bCardiovascular Research Unit, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh, UK, cDepartment of Cardiology, Stobhill Hospital, Balornock Road, Glasgow, UK
- 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 17 March 1998
Abstract
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.
