In vivo and in vitro response of corpus cavernosum to phosphodiesterase-5 inhibition in the hypercholesterolaemic rabbit.
OBJECTIVE
To investigate the effects of hypercholesterolaemia (HC) on rabbit corpus cavernosa in vivo and in vitro, and evaluate the efficacy of vardenafil and sildenafil in normal and HC rabbits, as the phosphodiesterase-5 (PDE-5) inhibitors vardenafil and sildenafil are widely used for treating erectile dysfunction (ED) and most organic causes of ED are associated with vascular risk factors like HC.


METHODS
Male New Zealand White rabbits were randomly divided into two groups; 11 HC rabbits were fed a 2% cholesterol diet, and 12 age-matched control rabbits received a regular diet. After 12-14 weeks, erectile responses to intravenous sodium nitroprusside (SNP) and PDE-5 inhibitors were evaluated for 2 h in conscious rabbits. Penile length was measured and the area under the curve calculated. Relaxant responses of corpus cavernosal strips to electrical-field stimulation (EFS) were measured before and after exposure to PDE-5 inhibitors and the nitric oxide synthase inhibitor N'-nitro-L-arginine methyl ester.


RESULTS
HC rabbits had a lower erectile response to SNP than controls; in both control and HC rabbits there was a greater erectile response after simultaneous exposure to SNP and vardenafil, or SNP and sildenafil. However, the responses of the HC rabbits were still significantly less than those of the controls. Corpora from control rabbits responded to EFS with greater relaxations at all frequencies, except 1 Hz. Corpora from both HC and control rabbits had greater responses to EFS after exposure to vardenafil and sildenafil; N'-nitro-L-arginine methyl ester diminished the response to EFS.


CONCLUSIONS
There was a significantly lower in vivo and in vitro erectile response in HC rabbits than in controls; erectile function measured in conscious rabbits can be used to assess quantitatively the efficacy of different agents, e.g. sildenafil and vardenafil, in pathological animals. In addition, both agents improve in vitro responses of erectile tissue from HC rabbits to EFS.
Firoozi
Farzeen
F
Division of Urology, Albany Medical College, Albany, NY 122083499, USA. Firoozf@mail.amc.edu
Longhurst
Penelope A
PA
White
Mark D
MD
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D019540:Area Under Curve; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007172:Erectile Dysfunction / Q000188:drug therapy; D006937:Hypercholesterolemia / Q000150:complications*; D007093:Imidazoles / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D014227:Triazines / Q000627:therapeutic use*; D000069058:Vardenafil Dihydrochloride
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5