Adrenergic facilitation by angiotensin: does it serve a physiological function?

A number of hormonal and pharmacological substances modulate adrenergic transmitter release by a presynaptic action (for reviews see Starke, 1977; Westfall, 1977). Prostaglandin E, acetylcholine, adenosine, dopamine and noradrenaline itself inhibit, whereas angiotensin II (ANG II), prostaglandin F 2d and isoproterenol enhance noradrenaline release. Thus stimulation of specific receptors by these substances can, through alteration in transmitter release, result in depression or augmentation, respectively, of adrenergic responses. Modulation is not limited to the adrenergic nerve terminal since with some of these agents an action on the postsynaptic site is also manifested (Malik, 1978; Verhaeghe, Lorenz, McGrath, Shepherd & Vanhoutte, 1978; Zimmerman, 1978). The purpose of this editorial review is to consider both peripheral and central adrenergic-modulating effects of angiotensin with respect to both the mechanism and the possible physiological importance. I shall not include discussion of adrenal medullary or ganglionic actions of ANG II. Early investigations demonstrated both central and peripheral adrenergic interactions of ANG II. When administered via the dog's carotid or vertebral arterial blood supply, ANG II elicited a pressor response which was found to be mediated over the sympathetic nerves (Bickerton & Buckley, 1961; Dickinson, 1965; Ferrario, Dickinson & McCubbin, 1970). It is not certain whether the pressor response is due to direct stimulation of vasomotor neurons or to facilitation of tonic excitatory activity. The influence of ANG II on peripheral adrenergic nerves is one of facilitation of evoked nerve activity and is not caused by a direct release of catecholamines (tyramine-like