Combined effect of sildenafil and guanethidine, propranolol or verapamil on erectile function in rats.
OBJECTIVE
This study aims to further elucidate the role of adrenergic transmission in erection and to highlight whether adrenergic transmission in the penis modulates sildenafil's action.


METHODS
Measurement of intracavernosal pressure in the anesthetized rat model.


RESULTS
Guanethidine (3 and 6 mg/kg) potentiated intracavernosal pressure/mean arterial pressure (ICP/MAP) rises in response to cavernous nerve stimulation by 4.375 ± 0.425 and 18.375 ± 1.085% respectively. Propranolol did the opposite. In presence of guanethidine, sildenafil (0.01, 0.1 and 1 mg/kg) potentiated ICP/MAP responses by 81.571 ± 4.918%, 147.83 ± 10.864% and 279.285 ± 23.053% at 1 Hz compared to 22.277 ± 2.139%, 123.571 ± 8.443% and 186.25 ± 13.542% respectively in the absence of guanethidine. Propranolol inhibited the effect sildenafil at all frequencies of stimulation. Verapamil exhibited a pro-erectile action and potentiated the effect of sildenafil (0.01, 0.1 and 1 mg/kg) on erectile responses corresponding to 85.25 ± 6.716%, 146 ± 11.288% and 221.571 ± 19.032% respectively compared to 26.011 ± 1.911%, 87.142 ± 8.73% and 182.2 ± 16.921% in its absence.


CONCLUSIONS
This study provides functional evidence that inhibition of sympathetic tone peripherally results in enhancement of erectile function. β-adrenergic receptors seem to play an important role in erection. The combination of sildenafil and guanethidine or verapamil could have a potential advantage on erectile function but propranolol may mask the effect of sildenafil on erectile function.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Amira M
AM
Senbel
Ahmed M
AM
Hashad
Fouad M
FM
Sharabi
Tahia T
TT
Daabees
D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006145:Guanethidine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D018663:Adrenergic Agents; D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011687:Purines; D011943:Receptors, Adrenergic, beta; D013450:Sulfones; D014665:Vasodilator Agents; D011433:Propranolol; D000068677:Sildenafil Citrate; D014700:Verapamil; D006145:Guanethidine