Angiotensin neuromodulation of adrenergic and purinergic co-transmission in the guinea-pig vas deferens.

1. The effects of angiotensin II (AII) and angiotensin III (AIII) on the isolated vas deferens of the guinea-pig were studied via three parameters: the overflow of adenosine 5'-triphosphate (ATP) and tritiated noradrenaline (NA), the mechanical response to field stimulation and the mechanical response to exogenous NA and alpha, beta-methylene ATP (alpha, beta-mATP). 2. At 2 Hz, AII enhanced the overflow of ATP and NA, whereas at 20 Hz, AII enhanced the overflow of NA but was without significant effect on ATP overflow. AIII, at 2 Hz, inhibited the overflow of ATP, but enhanced NA overflow, whereas at 20 Hz ATP overflow was unaffected, but NA overflow was still enhanced. 3. At 2 Hz, AII enhanced both phases of the response to field stimulation and at 20 Hz the overall response. AIII at 2 Hz enhanced the adrenergic response, but was without effect on the purinergic response to field stimulation. At 20 Hz, AIII was without effect on the overall response. 4. AII enhanced responses to exogenous NA and alpha, beta-mATP, whereas AIII was without effect. 5. These results provide evidence that both ATP and NA release are capable of being modulated by angiotensins. Furthermore, modulation of ATP release is frequency-dependent, whereas [3H]-NA release is not. These results raise questions about the mechanisms of storage and release of the sympathetic co-transmitters NA and ATP; they also show that angiotensin receptors in the guinea-pig vas deferens are not a homogeneous population.