Pre- and postsynaptic alpha-adrenoceptor antagonists: differentiated cardiovascular effects in the rat.

Intravenous (i.v.) injections of yohimbine, phentolamine, prazosine and phenoxybenzamine lowered blood pressure and increased heart rate in conscious rats. Intracerebroventricular (i.c.v.) injections of yohimbine and phentolamine increased blood pressure and heart rate; this was antogonized by pretreatment with clonidine. Phenoxybenzamine and prozosine had no effect or gave hypotension and tachycardia on i.c.v. injection. Pentobarbitone anaesthesia partly antagonized the cardiovascular effects of all alpha-adrenoceptor antagonist. Synthesis and utilization of central noradrenaline was increased by i.v. or i.c.v. yohimbine; anaesthesia partly antagonized this effect. In peripheral tissues others have found that yohimbine, tolazoline, piperoxan and phentolamine are potent blockers of the presynaptic alpha-adrenoceptors while phenoxybenzamine and prazosine act preferentially on postsynaptic alpha-adrenoceptors. The differentiated cardiovascular response to i.c.v. injection of these blockers may reflect their different affinity to central pre- and postsynaptic alpha-adrenoceptors.