Distribution Theory of Resistance of Neurogenic Vasoconstriction to Alpha-Receptor Blockade in the Rabbit

The effects of α-receptor-blocking agents on the contractile responses of isolated rabbit arteries to sympathetic nerve stimulation and exogenous l -norepinephrine ( l -NE) were compared. In the pulmonary artery and aorta, yohimbine, phentolamine, and phenoxybenzamine blocked the response to nerve stimulation less than that to an equipotent dose of l -NE. This resistance of neurogenic response was independent of the frequency and number of stimuli and persisted after inhibition of the nerve l -NE uptake by cocaine. The neurogenically released transmitter l -NE probably forms a high concentration near the adventitia-media junction, whereas the exogenous NE is distributed evenly throughout the thickness of media. Thus higher concentrations of α-receptor-blocking agents would be needed to block the effect of neurogenic l -NE than to block that of exogenous l -NE. This explanation of the resistance was thought to be more appropriate to the large vessels tested than that based on neuroeffector proximity.