Differential effects of drugs interacting with autonomic transmitters on responses of rat vas deferens to field stimulation.

Abstract

1. Frequency-response curves (0.1-30 Hz) were obtained in the epididymal portion of rat vas deferens. At low frequencies (0.1-1 Hz), the parameters evaluated were the first twitch and the fourth twitch at each frequency. The responses to trains of stimuli at intermediate (2-5 Hz) and high (10-30 Hz) frequencies were biphasic consisting of phase I (the first rapid phase of tetanus) and of phase II (the secondary slowly developing one). 2. Prazosin inhibited the first and the fourth twitch but not when the frequency was < 1 Hz. Suramin inhibited the first twitch while substantially depressing the fourth one. The combination of prazosin and suramin almost completely abolished all the twitches evoked by a train of stimuli at low frequencies. Nifedipine left almost unaltered the first twitch while markedly depressing the fourth one, especially at relatively high frequency (1 Hz). Verapamil was devoid of any inhibitory action. Papaverine depressed the first twitch while only at the highest concentration used (1 x 10(-4) M) markedly inhibited the fourth one. Chloroethylclonidine (CEC) depressed the first twitch and increased the fourth. 3. When intermediate (2-5 Hz) and high (10-30 Hz) frequencies are considered, prazosin and suramin partially inhibited both phase I and phase II, while in combination they almost completely abolished both phases. Nifedipine and verapamil selectively suppressed phase II, leaving phase I unaffected. Papaverine completely abolished both phase I and phase II. CEC was able to completely abolish phase I but increased phase II. 4. These results suggest that the response to the first twitch of a train at low frequency is prevailingly noradrenergic, prazosin-sensitive, while when the twitches are close enough (i.e. at 1 Hz) a summation of stimuli takes place and a predominant purinergic component, both suramin- and nifedipine-sensitive, becomes evident. 5. At high frequencies, both phases are due to the concomitant release of noradrenaline and adenosine triphosphate (ATP). The noradrenergic component of phase I is nifedipine-insensitive and CEC-sensitive, resembling the pharmacological profile of the endogenously released noradrenaline by single pulse, while that of phase II, nifedipine-sensitive and CEC-insensitive, is similar to that produced by exogenously applied noradrenaline.