ACTION OF PROPOFOL ON CENTRAL SYMPATHETIC MECHANISMS CONTROLLING BLOOD-PRESSURE

This study was done using Wistar rats lo determine if the actions of propofol (22 +/- 1, 40 +/- 2, 64 +/- 3 and 102 +/- 3 mg . kg-1 . hr-1) decreased blood pressure and heart rate through depression of brain stem vasomotor centres. All rats were given atropine to block vagal influences on the heart. Propofol decreased renal nerve activity as well as blood pressure and mean rate in a dose-dependent manner. Infusion of the lowest dose of propofol (22 +/- 1 mg . kg-1 . hr-1) had no effect on blood pressure, heart rate and renal nerve activity. Infusion of propofol at 40 +/- 2 mg . kg-1 . hr-1 decreased renal activity by 22 +/- 4% (mean +/- SEM) and at 64 +/- 3 mg . kg-1 . hr-1 it decreased renal nerve activity by 36 +/- 6%. Finally, infusion of the largest dose of propofol (102 +/- 3 mg - kg-1 . hr-1) decreased nerve activity by 50 +/- 5%. The haemodynamic changes observed in our experiments during the infusion of propofol paralleled the changes in sympathetic firing suggesting that hypotension was caused by central actions of propofol to depress sympathetic firing. In experiments with bolus injections of propofol, the renal nerve activity returned to normal before arterial pressure and heart rate recovered. Because decreases in blood pressure and heart rate were longer-lasting than changes in renal nerve activity, a part of the vasodepression and bradycardia caused by propofol likely resulted from direct actions on blood vessels and the heart. Sympathetic and cardiovascular responses to blocking neurons in the ventrolateral medulla with microinjection of glycine were depressed by propofol. However, responses to blockade of this important brainstem structure were elicited at all doses of propofol suggesting that, while it causes depression of CNS neurons responsible for control of resting arterial pressure and heart rate, this depression is not maximal and substantial control remains.