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

Abstract

The effects of a-receptor-blocking agents on the contractile responses of isolated rabbit arteries to sympathetic nerve stimulation and exogenous lnorepinephrine (Z-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 Z-NE. This resistance of neurogenic response was independent of the frequency and number of stimuli and persisted after inhibition of the nerve Z-NE uptake by cocaine. The neurogenically released transmitter Z-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 a-receptor-blocking agents would be needed to block the effect of neurogenic Z-NE than to block that of exogenous Z-NE. This explanation of the resistance was thought to be more appropriate to the large vessels tested than that based on neuroeffector proximity. KEY WORDSdistribution of NE phentolamine tunica media neuroeffector distance yohimbine smooth muscle phenoxybenzamine cocaine • In 1906, Dale (1) observed that ergot was less effective in blocking the effector response to sympathetic nervous activity than that to circulating epinephrine. Subsequently, parallel observations have been made with various areceptor blocking agents at many adrenergically innervated sites. In his review, Nickerson (2) concluded that all a-receptor-blocking agents appear to be more effective against responses to circulating sympathomimetic agents than against responses to sympathetic nervous activity. All degrees of relative effectiveness of a-receptor-blocking agents against these two types of responses may be found at different sites in the body. With the exception of Levin and Beck (3) and Urquilla et al. (4),

Inactivation of Endogenous Noradrenaline Released by Electrical Stimulation <i>in vitro</i> of Dog Saphenous Vein

“…However, W yse and Beck [1972] have questioned the applicability of this principle to vascular tissue. Our results show that the traditional principle is applicable to the saphenous veins of the dog, confirming the results of Lju n g [1969] and Bevan and Su [1971] using other vascular tissue.…”

Isolated Human Cystic Artery: Responses to Common Agonist and Antagonist Drugs

“…The easily available umbilical vessels have been more widely used than others, but present the disadvantage that they are not innervated (Eltherington et aL, 1968). Two cursory comparisons o f responses o f isolated temporal artery (Horwitz et al, 1974) and isolated renal vein (Schmidt et aL, 1978) (Bevan and Su, 1971) but is not seen with phenoxybenzamine ( Wyse andBeck, 1972, 1973), a-adrenergic-blocking agent with a different mechanism o f action. Preliminary ob servations with phenoxybenzamine indicate the same discrepancy exists in human cystic artery.…”

Comparison of the antagonistic effects of phentolamine on vasoconstrictor responses to exogenous and neurally released noradrenaline in vivo

“…This difference in susceptibility has been traditionally explained on the basis that the high concentration of noradrenaline produced in the subjunctional cleft following release from neuronal varicosities is sufficient to displace partially the antagonist from its binding sites on the subjunctional a-adrenoceptors (Ljung, 1969;Bevan & Su, 1971;Krnjevic, 1974).…”