Comparison of the antagonistic effects of phentolamine on vasoconstrictor responses to exogenous and neurally released noradrenaline in vivo

Abstract

The antagonistic effects of the alpha-adrenoceptor blocking agent phentolamine on vasoconstrictor responses to intraluminal noradrenaline and lumbar sympathetic nerve stimulation were compared in the hindlimb of the anaesthetized dog. Sympathetic stimulation with 1 pulse or trains of 4-10 pulses at 0.4-40 Hz produced graded vasoconstrictor responses that were matched in amplitude by intra-arterial injections of 10(-8) - 10(-6) g noradrenaline. Phentolamine (0.5 mg kg-1 i.v.) attenuated amplitude-matched responses to both types of stimuli to quite similar extents. The extent of the effect of phentolamine on neurogenic responses was greater with 1 pulse stimulation than with trains, and greater with 4 pulse than with 10 pulse trains. The effect was maximal within 2 min of phentolamine administration and wore off in parallel with that on responses to injected noradrenaline. The results are consistent with the view that transmitter released from noradrenergic vasoconstrictor nerves acts primarily on subjunctional alpha-adrenoceptors.