Mechanism of Enhancement by Angiotensin II of Sympathetic Adrenergic Transmission in the Guinea Pig

An electrophysiological analysis was made of the mechanism underlying the potentiation by angiotensin II of responses to adrenergic nervous stimulation of the isolated vas deferens and the uterine artery of the guinea pig. Concentrations of angiotensin II up to 5 x 10 -7 g/ml did not affect resting muscle cell membrane potential, cause spontaneous transmitter release, or increase transmitter release induced by single nerve stimuli. The time courses of excitatory junction potentials were not increased, indicating that the neuronal mechanism for transmitter inactivation was not inhibited. Angiotensin II did, however, increase the degree of facilitation of successive excitatory junction potentials during repetitive low-frequency nerve stimulation, leading to greater depolarization of the muscle cells than under control conditions. That this enhancement of facilitation was the primary mechanism underlying potentiation of transmission by angiotensin II was supported by the finding that the potentiation of mechanical responses to nerve stimulation decreased markedly as the frequency of stimulation was raised over the range where facilitation is replaced by summation as the major factor in depolarizing the muscle cells to firing threshold (2-6 pulses/sec). This mechanism of action of angiotensin II means that its potentiating effect on transmission is relatively specific for the low frequencies of nervous activity which are thought to be important in tonic cardiovascular control.