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Keywords:

  • α1-adrenoceptors;
  • alfuzosin;
  • corpus cavernosum;
  • rabbit penis;
  • benign prostatic hypertrophy

OBJECTIVE

To compare the direct relaxant effects of alfuzosin, phentolamine and sildenafil in rabbit isolated corpus cavernosum (CC) pre-contracted with phenylephrine or KCl.

MATERIALS AND METHODS

Penile erectile tissue was obtained from male New Zealand White rabbits (22–26 weeks old). The CC was cut into longitudinal strips and mounted under 2 g resting tension in 5-mL jacketed organ baths containing a modified Krebs solution bubbled with 95% O2, 5% CO2 and maintained at 37 °C. Tissue strips were pre-contracted by 60 mmol/L KCl or 10 µmol/L phenylephrine. After obtaining a stable plateau of contractions, test compounds were added to the organ bath. The relaxant potencies were expressed as the percentage of inhibition of the plateau of contraction induced by 10 µmol/L phenylephrine.

RESULTS

Alfuzosin showed a concentration-dependent relaxing effect on rabbit CC pre-contracted by 10 µmol/L phenylephrine, with a mean (sd) pIC50 of 7.64 (0.06). The relaxant effect was unaffected by pre-incubation with 100 µmol/L Nω-nitro-l-arginine methyl ester (L-NAME). Phentolamine had a potency similar to alfuzosin, with a pIC50 of 7.44 (0.08). Both alfuzosin and phentolamine were completely ineffective on the plateau of contraction induced by 60 mmol/L KCl. In contrast to alfuzosin, sildenafil was equipotent in relaxing the rabbit CC against each contractile agent, with pIC50 values of 7.25 (0.09) and 7.23 (0.22) with 10 µmol/L phenylephrine and 60 mmol/L KCl, respectively. The relaxant response to sildenafil was partly blocked by pretreatment with 100 µmol/L L-NAME, with pIC50 values of 7.94 (0.09) and 6.63 (0.32) without and with L-NAME, respectively. Sildenafil, incubated for 45 min at 10 µmol/L, had no relaxant effect on the resting tension of the preparation or on the concentration-response curve to phenylephrine.

CONCLUSIONS

The direct relaxant effect of alfuzosin is mediated through α1-adrenoceptor blockade. The relaxations induced by phentolamine and alfuzosin are independent of nitric oxide, whereas those induced by sildenafil are, at least partly, sensitive to L-NAME and a selective soluble guanylate cyclase inhibitor, indicating the involvement of nitric oxide and soluble guanylate cyclase. Alfuzosin and phentolamine effectively counteract α1-adrenoceptor-mediated contractions of rabbit CC. If valid for human CC, such an effect may contribute to an improved erectile function in patients treated for benign prostatic hyperplasia.