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

Int J Impot Res. 1998 Dec;10(4):215-23. doi: 10.1038/sj.ijir.3900351.

Abstract

Aim of the study: We investigated the biochemical and physiological mechanisms of action of phentolamine mesylate (Vasomax) 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. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / metabolism
  • Animals
  • Binding, Competitive
  • Cell-Free System
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Male
  • Muscle Relaxation / drug effects*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Penis / drug effects*
  • Phentolamine / metabolism
  • Phentolamine / pharmacology*
  • Rabbits
  • Receptors, Adrenergic, alpha / physiology*

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Enzyme Inhibitors
  • Receptors, Adrenergic, alpha
  • Nitroarginine
  • Nitric Oxide Synthase
  • Phentolamine