Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms.
OBJECTIVE
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.
Traish
A
A
Department of Urology, Boston University School of Medicine, MA 02118, USA.
Gupta
S
S
Gallant
C
C
Huang
Y H
YH
Goldstein
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002474:Cell-Free System; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010413:Penis / Q000187:drug effects*; D010646:Phentolamine / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D011942:Receptors, Adrenergic, alpha; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D010646:Phentolamine