Role of ATP-sensitive K+ channels in relaxation of penile resistance arteries.
OBJECTIVE
To investigate the functional presence of adenosine triphosphate (ATP)-sensitive potassium (K+) channels (K(ATP)) in penile resistance arteries by evaluating the relaxant effects of the selective K(ATP) channel openers, cromakalim and levcromakalim, and also the involvement of K(ATP) channels in the relaxation of two drugs currently used in the treatment of erectile dysfunction (ie, prostaglandin E1 [PGE1] and sildenafil).


METHODS
Penile resistance arteries were dissected from the horse corpus cavernosum and mounted in microvascular myographs for isometric tension recording. The arteries were precontracted with phenylephrine, and the responses to several vasodilators were tested in the absence and presence of K+ channel blockers.


RESULTS
Cromakalim and levcromakalim evoked complete concentration-dependent relaxations that were blocked by 3 microm of the selective K(ATP) channel inhibitor glibenclamide. Raising extracellular K+ (25 mM) inhibited the relaxations to PGE1 and to the selective inhibitor of the cyclic adenosine monophosphate-specific phosphodiesterase (PDE4) rolipram. At a concentration selective for calcium-activated K+(K(Ca)) channels (3 mM), tetraethylammonium inhibited rolipram responses but not those of PGE1. However, glibenclamide significantly reduced the relaxation to both PGE1 and rolipram, but not those induced by the selective inhibitor of the type 5 cyclic guanosine monophosphate-specific phosphodiesterase (PDE5).


CONCLUSIONS
The present results suggest a functional role for K(ATP) channels in the relaxation of penile resistance arteries, as well as their differential involvement in the vasodilation to drugs used in the treatment of organic erectile dysfunction. They mediated relaxation to PGE1 and cyclic adenosine monophosphate-elevating agents, but not those of cyclic guanosine monophosphate-elevating agents such as sildenafil.
Ruiz Rubio
José L
JL
Departamento de Urología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Hernández
Medardo
M
Rivera de los Arcos
Luis
L
Benedito
Sara
S
Recio
Paz
P
García
Pilar
P
García-Sacristán
Albino
A
Prieto
Dolores
D
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology*; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D006736:Horses; D006801:Humans; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000098:blood supply* / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011458:Prostaglandins E / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D010879:Piperazines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011458:Prostaglandins E; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate; D000068677:Sildenafil Citrate; D005905:Glyburide