Effects of sildenafil on human penile blood vessels.
OBJECTIVE
To investigate the effects of sildenafil on human penile blood vessels and evaluate the interaction of sildenafil with neurogenic-mediated responses. Sildenafil is currently used in the treatment of erectile dysfunction.


METHODS
Penile dorsal arteries and deep dorsal veins were obtained from 14 multiorgan donors. Vascular rings were suspended in organ bath chambers, and the isometric tension was recorded. We then studied the effects of sildenafil on precontracted vessels and the neurogenic (noradrenergic and nitrergic) responses.


RESULTS
Sildenafil (10(-9) to 3 x 10(-6) M) caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprusside. Relaxation was unaffected by the inhibitor of nitric oxide synthase N(G)-monomethyl-L-arginine (10(-4) M). Compared with zaprinast, sildenafil was 8 to 10 times more potent in terms of the median effective concentration (EC(50)) values. Electrical field stimulation of the vessels under resting tension caused frequency-dependent contractions that were attenuated in the presence of sildenafil. When penile vessels were contracted after blockade of norepinephrine release with guanethidine (10(-6) M), electrical stimulation induced frequency-dependent, nitric oxide-dependent relaxations that were enhanced by sildenafil.


CONCLUSIONS
These results indicate that the relaxation of human penile arteries and veins induced by sildenafil involves inhibition of noradrenergic contraction, enhancement of neurogenic nitric oxide-mediated relaxation, and inhibition of smooth muscle contraction.
Medina
P
P
Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
Segarra
G
G
Vila
J M
JM
Domenech
C
C
Martínez-León
J B
JB
Lluch
S
S
D000293:Adolescent; D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000294:innervation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000098:blood supply*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014680:Veins / Q000187:drug effects / Q000294:innervation
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate