Augmented chemosensitivity has been observed in chronic heart failure (CHF: Sun et al, 1999) and its subsequent effects, including sympathetic hyperactivity have been shown to be instrumental in the progression of the disease (Ponikowski et al, 2001). We have investigated the role of plasma catecholamines in the chemosensitivity in CHF. CHF was induced in male wistar rats (200-300g) following administration of isoprotenerol by osmotic mini-pump which was implanted under inhalation anaesthesia (isoflurane 3.5% in oxygen) with subsequent pain relief administered as required (Temgesic, s.c. administration) (10 days – 4mg/kg/day s.c., Alzet mini pump). At 10 days, animals were instrumented, under anaesthesia (urethane, 1.4g/kg i.p.), to measure ventilation and arterial blood pressure. Acute experiments were performed on CHF (n=6) and normal rats (n=9) to assess the cardiovascular and respiratory responses to acute hypoxia (incremental reduction of inspired gases to 10% oxygen, balance nitrogen) under 3 conditions: Control (no infusion); supplemental noradrenaline infusion (10ug/kg/min) and after administration of the beta adrenoreceptor antagonist, propranolol (1mg/kg). Exponential functions with offset were fitted to all ventilatory response curves. Values are means ± S.E.M. and compared by ANOVA with significance as p<0.05. Infusion of NA to normal animals augmented ventilation at all concentrations of inspired oxygen, but particularly in hypoxia (112.3±6.1 vs. 78.4±6.6 ml/min at 100mmHg PaO2, P<0.05. 178.0±7.6 vs. 128.5±8.3 ml/min at 50mmHg PaO2, P<0.05, in the noradrenaline and control responses respectively). Subsequent administration of propranolol returned the NA augmented ventilation back to the control hypoxia response in normal animals. CHF rats had an elevated ventilatory response to hypoxia (to 156.3±9.5 ml/min at 50mmHg PaO2, P<0.05, compared to normal rats). Infusion of NA to CHF rats was without effect, indicating maximal adrenoreceptor activation has already occurred such that the elevation in ventilatory response to NA was significantly attenuated compared to the normal animals (0.9±8.5 vs. 49.6±7.6 ml/min in CHF and normal, respectively at 50mmHg PaO2, P<0.05). Propranolol attenuated the ventilatory response to a greater extent in the CHF rats than in normal rats, confirming a higher resting level of tonic catecholamine activity in CHF (43.7± 7.5 vs. 21.1±5.9 ml/min at 50mmHg PaO2, P<0.05). This may support the value of using beta-adrenoceptor antagonism in the management of CHF. Bilateral carotid sinus nerve section (CSNX) in normal rats (n=6) blunted the ventilatory response to NA by 20% (139.8±11.5 vs. 174.9±16.2 ml/min, P<0.05). These results suggest that NA may act directly upon carotid chemoreceptors to increase chemosensitivity and hence augment ventilation in CHF that could be alleviated by beta-blocker.