Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms

Aim of the study: We investigated the biochemical and physiological mechani sms of action of phentolamine mesylate (Vasomax(TM)) in regulating erectile tissue smooth muscle contractility in human and rabbit corpus cavernosum. Methods: The binding activity of phentolamine was investigated in a cell-fr ee system by displacement of specific and selective radiolabelled ligands t o alpha 1 and 2 adrenergic receptors. The physiologic activity of phentolam ine-mediated relaxation of adrenergic and non-adrenergic pre-contracted ere ctile tissue strips of human and rabbit corpus cavernosum were studied in o rgan bath chambers. Results: In corpus cavernosum membranes,phentolamine displaced binding of t he selective alpha 1 receptor antagonists [I-125]HEAT and [H-3]prazosin and the alpha 2 receptor antagonists [H-3]rauwolscine and [H-3]RX 821002 with relatively high affinity. Phentolamine caused concentration dependent relax ation in erectile tissue strips pre-contracted with adrenergic agonists phe nylephrine, norepinephrine, oxymetazoline and UK 14 304, as well as with no nadrenergic contractile agents endothelin and KCl. Biochemical and physiolo gic studies reveal that the concentration of phentolamine required to displ ace half maximal binding or to produce half-maximal relaxation was similar to that found in human plasma 30 min after ingestion of 40 mg of Vasomax(TM ), Reversible inhibition of nitric oxide synthase by L-nitroarginine or mec hanical disruption of endothelium diminished non-adrenergic phentolamine-me diated erectile tissue relaxation. Conclusions: Phentolamine mesylate induced relaxation of corpus cavernosum erectile tissue by direct antagonism of alpha 1 and 2 adrenergic receptors and by indirect functional antagonism via a non-adrenergic, endothelium-med iated mechanism suggesting nitric oxide synthase activation.