INHIBITION OF SYMPATHETIC TRANSMISSION IN RAT-HEART BY CLONIDINE - ROLES OF STIMULATION FREQUENCY, ENDOGENOUS FEEDBACK AND NORADRENALINE RE-UPTAKE

The inhibitory effects of clonidine were compared with other procedures which reduce the effector response to sympathetic cardioaccelerator nerve stimulation in the pithed rat. The effect of clonidine was most marked against responses to stimulation with relatively short trains of pulses and/or low frequencies of stimulation but a similar effect could be achieved by stimulating fewer fibres, by pretreating the rats with reserpine or by acute administration of guanethidine or propranolol. Unlike the other procedures, however, clonidine did not abolish responses. The effects of clonidine were similar whether or not endogenous α-adrenoceptor-mediated feedback could be demonstrated. After blockade with cocaine of the neuronal re-uptake of transmitter noradrenaline, the inhibitory effect of clonidine was undiminished when the effect of cocaine on the frequency/response curve was taken into account. It is concluded that with frequencies and train lengths within the physiological range relative resistance to the inhibitory effect of clonidine is more dependent on post-junctional summation than on the development of pre-junctional facilitation or feedback mechanisms. Even with a single stimulus, however, the inhibitory effect of clonidine was limited suggesting that a portion of transmitter release is inaccessible to such blockade. © 1979 Springer-Verlag.