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© Copyright 2004 The British Pharmacological Society

204P GKT, University of London
Winter Meeting December 2003

Relation between beta-2 adrenoceptor responsiveness assessed by pulse wave analysis and flow mediated dilation

C. Rambaran, E. Iveson, I. L. Williams, B. Jiang, P. J. Chowienczyk, J. M. Ritter, A. M. Shah, T. Forrester & L. Kalra. Cardiovascular Research Group, Guy's,King's and St. Thomas' School of Medicine ,King's College London and Tropical Medicine Research Institute University of the West Indies, Kingston, Mona, Jamaica.

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Rambaran C
Iveson E
Williams IL
Jiang B
Chowienczyk PJ
Ritter JM
Shah AM
Forrester T
Kalra L

Vasodilator responses to ß2-adrenoreceptor agonists are mediated, at least in part, by endothelium-derived nitric oxide (NO) and the use of pulse wave analysis to measure the response to systemic administration of a ß2-agonist has been proposed as a simple means to assess endothelial function (Chowienczyk et al. 1999; Wilkinson et al. 2002). The purpose of the present study was to examine the correlation between the response of the digital volume pulse to the ß2-agonist albuterol and flow mediated NO-dependent, dilation (FMD) of the brachial artery.

FMD and pulse wave responses to albuterol were determined on separate occasions within one week in 40 healthy subjects (18 women), aged 53 ± 15years . Measurements were made in a temperature-controlled laboratory in the morning after an overnight fast and after subjects had rested supine for 30 minutes. Baseline measurements revealed, systolic blood pressure (132 ± 16 mmHg), diastolic blood pressure (76± 10 mmHg) and total cholesterol (5.0± 1.0 mmol/l.), means ± SD. FMD was measured using high resolution ultrasound (HDI 5000, ATL) and automatic wall tracking software (HDI lab, ATL) and expressed as % dilation of the brachial artery after reactive hyperaemia (Corretti et al. 2002). Pulse wave analysis (DVP, Pulse Trace, Micro Medical). The DVP was measured at baseline and during intravenous infusion of albuterol (5mg/min, for 15 min). The relative height of the early diastolic peak of the DVP, an index of pressure wave reflection (RI), was computed from the DVP and the change, from baseline, (RI) used as a measure of the response to albuterol. The correlation between RI and FMD was examined using Pearson's test of correlation. The sensitivity and specificity of RI to detect normal (FMD > 8%) and abnormal endothelial function (FMD < 4%) was determined using a receiver operating characteristic (ROC) plot. The study was approved by King's College Hospital Research Ethics Committee.

Mean values (±SE) of FMD and RI were 6.12 ±(0.53)% and 7.9 ±(1.2)% respectively. RI was significantly correlated with FMD (R=0.42, P<0.01). Using a cut-off value of 8% for RI, the DVP response to albuterol had >80% sensitivity and >70% specificity to detect normal or abnormal endothelial function (as defined by FMD).

These results suggest that the pulse wave response to albuterol can be used to detect endothelial dysfunction characterised by impaired FMD. Use of ß2 agonist as a probe of endothelial function offers the potential for use in large scale studies.

Chowienczyk PJ et al.( 1999) J Am Coll Cardiol. 34: 2007-2014.
Corretti MC et al.(2002) J Am Coll Cardiol. 39:257-265.
Wilkinson IB et al.( 2002) Arterioscler Thromb Vasc Biol. 22:147-152.