Effects of oral labetalol on forearm and hepatic circulations in normotensive humans.

The effects of single oral labetalol doses (100, 200, and 400 mg) on forearm and hepatic circulations were studied over a 2-hour period in 27 normotensive human subjects by using a double-blind, placebo-controlled design. Labetalol administration resulted in a dose-dependent beta-receptor blockade as determined by an isoproterenol sensitivity test. It also produced a dose-dependent decrease in mean arterial blood pressure that was of greater duration at larger doses. At the lowest dose labetalol produced a transient decrease in arterial pressure followed by a decrease in forearm blood flow and increase in forearm vascular resistance. As the dose of labetalol increased, the hypotensive response became more prolonged, but the changes in forearm blood flow and vascular resistance no longer occurred. Heart rate did not change significantly after any of these doses. Hepatic blood flow also did not change significantly after labetalol. Our results suggest that the increase in forearm vascular resistance after the lowest dose of labetalol probably was caused by unopposed alpha-receptor activation because the agent had a relatively greater beta-receptor blocking action at the low doses, but as the dose increased the alpha-receptor blocking action of the drug became more pronounced and abolished the vasoconstrictor effect in the forearm. Furthermore, our study indicates that despite the significant drop in arterial pressure at doses greater than 100 mg, blood flow is well maintained to the skeletal muscle and splanchnic circulations during labetalol therapy.