The effects of hypoglycaemia during hyperinsulinaemia, occurring under various pathophysiological conditions, on the cardiovascular regulatory system and vasculature are largely unknown. The aim of the present study was to investigate regulatory and haemodynamic responses to acute hyperinsulinaemia and consequent hypoglycaemia in 18 healthy subjects. Blood sampling and 5 min ECG and blood pressure recordings were performed at baseline and during the euglycaemic and hypoglycaemic phases of a hyperinsulinaemic clamp. Heart rate variability (HRV) and blood pressure variability (BPV) were assessed by using power spectral analysis, and baroreflex sensitivity (BRS) was assessed using the cross-spectral method. Stroke volume was assessed from the non-invasive blood pressure signal by the arterial pulse contour method. Euglycaemic hyperinsulinaemia did not change plasma catecholamine concentrations, HRV, BPV, BRS, heart rate, blood pressure, stroke volume, cardiac output or peripheral resistance. However, hyperinsulinaemic hypoglycaemia resulted in an 11.7-fold increase in the plasma adrenaline concentration (from 0.19±0.03 to 1.68±0.32 nmol/l; P<0.001), and a modest 1.3-fold increase in the plasma noradrenaline concentration (from 1.74±0.22 to 2.02±0.19 nmol/l; P<0.05) compared with baseline. Furthermore, we observed significant decreases in diastolic blood pressure (from 68±3 to 60±3 mmHg; P<0.05) and peripheral resistance (from 24.1±1.2 to 18.5±1.1 mmHg·min-1·l-1; P<0.01). Stroke volume and cardiac output increased markedly from the euglycaemic to the hypoglycaemic period only (P<0.01 for both). Hypoglycaemia did not influence HRV, BPV or BRS. Our findings indicate that hyperinsulinaemic hypoglycaemia is characterized by a significant increase in the plasma adrenaline concentration and by decreases in peripheral resistance and blood pressure. Counter-regulation during hyperinsulinaemic hypoglycaemia involves selective adrenomedullary sympathetic activation, and does not influence cardiac parasympathetic regulation or baroreflex control of heart rate.

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