Synergistic effect of propranolol and nicotinic acid on the inhibition of plasma free fatty acid release in the dog.

Fatty acid mobilization was effected in 24 anesthetized dogs by infusion of norepinephrine over a four-hour period. Infusions of propranolol and nicotinic acid at various doses, individually and in combination, were added and free fatty acid levels were serially determined. Synergistic action of the two agents was apparent in that minimally effective concentrations of the two agents when used in combination suppressed the release of free fatty acids to 29 percent of levels achieved with norepinephrine (1,186 ju,Eq/L) and 70 percent of levels in saline control animals (501 /j.Eq/L). Large individual doses were no more effective than low doses used in combination. The synergistic action of propranolol and nicotinic acid in the suppression of free fatty acid mobilization may be explained by the action of these two agents on the inhibition of the adenyl cyclase system of the adipose tissue cell. This synergistic action in reducing plasma free fatty acids and their effect on lipid synthesis would allow the use of smaller doses that could reduce the risk of side effects.