EFFECTS OF PRAZOSIN, PHENTOLAMINE AND YOHIMBINE ON NORADRENERGIC TRANSMISSION IN THE RAT RIGHT VENTRICLE IN VITRO

1 The effects of prazosin, phentolamine and yohimbine on the accumulation of radioactivity from [3H]-noradrenaline, and on the subsequent spontaneous and field stimulation-evoked outflow of radioactivity have been investigated in the rat right ventricle in vitro. In addition the effects of these agents on contractions produced by exogenous amines or by field stimulation are reported. 2 Prazosin, phentolamine and yohimbine had no effect on the accumulation of radioactivity from [3H]-noradrenaline. 3 The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]-noradrenaline, was reduced by prazosin (1 times 10-8 or 1 times 10-7M) and 1 times 10-6M yohimbine. Phentolamine and 1 times 10-7M yohimbine had no effect on the spontaneous outflow of radioactivity. 4 Prazosin, phentolamine and yohimbine (all at 1 times 10-7M) reduced the decline in outflow of radioactivity evoked by field stimulation at 5Hz. In the presence of yohimbine, prazosin or phentolamine had no effect on the evoked outflow. The effect of prazosin, phentolamine and yohimbine alone probably represents antagonism at prejunctional α-adrenoreceptors. 5 The rate of beating and force of contractions evoked by 1 times 10-6M isoprenaline were not altered by prazosin, phentolamine or 1 times 10-7M yohimbine. The rate of beating evoked by noradrenaline (1 times 10-6M) was reduced by prazosin and phentolamine. Yohimbine (1 times 10-6M) reduced the rate of beating to isoprenaline and to noradrenaline. These effects of prazosin and phentolamine probably represent antagonism at postjunctional α1-adrenoreceptors and that of yohimbine a decrease in the excitability of the postjunctional membrane. 6 In the control tissues the force of contractions evoked by field stimulation at 5Hz declined slowly with successive stimulations at 30 min intervals. In the presence of prazosin (1 times 10-8 and 1 times 10-7M), phentolamine (1 times 10-7 and 1 times 10-6M) and 1 times 10-7M yohimbine the responses did not decline with successive stimulations. Yohimbine (1 times 10-6M) had no effect on the stimulation-evoked responses. 7 Phentolamine or yohimbine (both at 1 times 10-7M) had no additional effect on the stimulation-evoked responses in the presence of prazosin (1 times 10-7M). Prazosin (1 times 10-8M) and yohimbine (1 times 10-7M) had no further effect in the presence of phentolamine (1 times 10-6M). Prazosin or phentolamine (both at 1 times 10-7M) had no effect on stimulation-evoked responses in the presence of yohimbine (1 times 10-7M). 8 In the rat right ventricle, the ability of phentolamine and yohimbine to prevent the decline in the stimulation-evoked responses with successive stimulations is probably due to antagonism at prejunctional α-adrenoreceptors. However it is suggested that the ability of prazosin to prevent the decline in response is due to a release of endogenous noradrenaline and to antagonism at prejunctional α-adrenoreceptors.