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

Abstract

Aim of the study: We investigated the biochemical and physiological mechanisms 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-free system by displacement of specific and selective radiolabelled ligands to alpha 1 and 2 adrenergic receptors. The physiologic activity of phentolamine-mediated relaxation of adrenergic and non-adrenergic pre-contracted erectile tissue strips of human and rabbit corpus cavernosum were studied in organ bath chambers.

Results: In corpus cavernosum membranes, phentolamine displaced binding of the selective alpha 1 receptor antagonists [¹²⁵I]HEAT and [³H]prazosin and the alpha 2 receptor antagonists [³H]rauwolscine and [³H]RX 821002 with relatively high affinity. Phentolamine caused concentration dependent relaxation in erectile tissue strips pre-contracted with adrenergic agonists phenylephrine, norepinephrine, oxymetazoline and UK 14 304, as well as with non-adrenergic contractile agents endothelin and KCl. Biochemical and physiologic studies reveal that the concentration of phentolamine required to displace 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 mechanical disruption of endothelium diminished non-adrenergic phentolamine-mediated 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-mediated mechanism suggesting nitric oxide synthase activation.