Guanethidine and guanacline on the rat vas deferens

1 In acute experiments guanethidine was considerably more potent than guanacline in reducing contractile responses of the rat vas deferens to electrical stimulation of intramural nerves.2 Chronic treatment of rats for 19 weeks with guanethidine (5mg/kg, daily) reduced responses to electrical stimulation to 25% of control, potentiated responses to exogenous noradrenaline and depleted endogenous noradrenaline.3 After cessation of guanethidine treatment responses to electrical stimulation increased to 60% of control (in one week) but showed no further increase. There was no decrease in the potentiation of exogenous noradrenaline (after 14 weeks) nor any increase in endogenous noradrenaline levels (after 7 weeks).4 Chronic treatment of rats for 19 weeks with guanacline (5mg/kg, daily) potentiated responses to exogenous noradrenaline and depleted endogenous noradrenaline as much as guanethidine treatment but did not reduce responses to electrical stimulation.5 On cessation of guanacline treatment there was some increase in noradrenaline content (after 2 to 3 weeks) and some decrease of potentiated responses to exogenous noradrenaline (after 2 weeks).6 The noradrenaline-depleting action of these drugs is distinct from blockade of nerve-mediated responses in the rat vas deferens and contractile function after guanethidine treatment can be partly restored despite persistence of noradrenaline depletion and supersensitivity.