Circulatory effects of noradrenaline and adrenaline before and after labetalol.

Two studies were carried out in the same six normal healthy males to compare the circulatory effects of exogenously infused noradrenaline and adrenaline before and after intravenous labetalol. Noradrenaline before and after labetalol produced a similar pattern of circulatory change, namely dose related systolic and diastolic pressor responses accompanied by profound bradycardia and reduced cardiac output. Labetalol competitively antagonized both the systolic and diastolic pressor effects of noradrenaline. Adrenaline at low doses produced a diastolic depressor response accompanied by increases in heart rate and cardiac output. The highest dose also produced smaller increases in heart rate and cardiac output and diastolic pressure increased slightly. All doses provoked increases in systolic pressure. After labetalol all doses of adrenaline provoked a diastolic pressor response which was marked at high doses. The systolic response was attenuated compared with that before labetalol. At all doses, heart rate and cardiac output were reduced. Since in the presence of labetalol both noradrenaline and adrenaline profoundly reduce heart rate and cardiac output whilst increasing blood pressure, it may be unwise to use either of these catecholamines alone if attempts are being made to reverse excessive hypotension from labetalol overdose. Preliminary observations indicate that labetalol does not increase endogenous plasma catecholamines immediately after intravenous injection. Plasma concentrations of noradrenaline and adrenaline after exogenous infusion were increased after labetalol compared with those levels before labetalol. It appears that labetalol inhibits the clearance of catecholamines from the plasma possibly by inhibiting neuronal uptake mechanisms.