EVIDENCE FOR THE ROLE OF PERIPHERAL a-2 RECEPTORS
IN REDUCING NORADRENALINE RELEASE. A. Aggarwal*, E. Socratous, M. Esler, D.
Kaye. Neurocardiology Laboratory, Alfred Baker
Medical Unit, Prahran, Vic. Background:
Clonidine, an a-2 agonist, has been shown to have beneficial
haemodynamic effects and to decrease noradrenaline (NE) release in patients
with heart failure. Whilst its action
is presumed to be mediated via the a-2 receptors in the central nervous system (CNS), the
degree to which is may act upon peripheral pre-synaptic a-2 receptors, is
unclear. If these receptors are
functionally important, then future drug therapy may be developed to target
these and thereby allay the side effects of CNS stimulation such as sedation
and depression. Methods: 18
healthy volunteers and 7 patients with heart failure (CHF) received
intra-arterial (IA) clonidine into the brachial artery (0.48 mg/min/100ml
forearm for 5 minutes). Using the
techniques of strain-gauge plethysmography and radiotracer kinetics, we then
measured forearm blood flow (FBF) and forearm noradrenaline spillover (FSO). Results: From
baseline, IA clonidine caused a 27% and 35% reduction in FBF in the healthy and
CHF groups respectively. However, only
in the healthy group was a significant reduction (45%) in FSO demonstrated
(p<0.001). Recognising the flow
dependence of FSO, we also calculated the Plasma Appearance Rate of NE. Again,
only in the healthy group was there a significant reduction seen (p=0.002). Conclusions:
Peripheral a-2
receptors are functionally important in inhibiting NE release. This effect is
not entirely flow dependent, especially as the CHF group had a larger reduction
in flow with no significant decrease in FSO.
In CHF, there may be a reduction in the number and/or function of
peripheral a-2
receptors.
