Controversial evidence regarding the functional importance of presynaptic alpha receptors.

alpha-Adrenergic agonists have been reported to decrease the release of neuronal norepinephrine (NE) via presynaptic alpha 2 receptors when studied under in vitro conditions. Within the last several years studies have been performed in the intact animal to determine whether this presynaptic mechanism is a pharmacological artifact or whether it plays a functional role in cardiovascular physiology. In the intact renal vascular bed clonidine, oxymetazoline, and NE did not decrease stimulation-induced vasoconstrictor responses relative to constrictor responses produced by exogenous NE. Similarly, the alpha-receptor antagonists yohimbine and phentolamine did not potentiate constrictor responses induced by renal nerve stimulation. Studies involving the heart produce contradictory results. Clonidine and NE have been reported to decrease or have no effect on chronotropic responses to cardiac nerve stimulation. Phenoxybenzamine and desipramine have been reported to increase the overflow of NE in coronary sinus blood during cardiac nerve stimulation but not to potentiate chronotropic responses. Thus, this brief review points out that the functional importance of a presynaptic mechanism to modulate the release of NE still remains to be determined.