Treatment with hypotensive agents affects the impaired relaxation of the penile corpus cavernosum in hypertensive rats.
Treatment of erectile dysfunction (ED) in hypertensive subjects remains to be formally established. There is currently no standardized treatment for ED in hypertensive subjects. In this study, we tested our hypothesis that hypotensive drugs would improve impaired relaxation in the corpus cavernosum of spontaneously hypertensive rats (SHR). Ten-week-old SHR was treated with amlodipine, imidapril or hydralazine for 4 weeks. Although all three drugs achieved an equivalent decrease in systolic blood pressure (SBP), only amlodipine and imidapril induced an increase in relaxation in response to electrical field stimulation (EFS) of the corpus cavernosum. In the case of amlodipine, this effect was dose- and SBP-dependent. Nitric oxide (NO)-dependent relaxation was increased by amlodipine over a wide range of EFS frequencies, was increased by imidapril at low EFS frequencies, and was decreased by hydralazine. Carbon monoxide (CO)-dependent relaxation was only increased by hydralazine, and this increase occurred over a wide range of frequencies. The NOx and cGMP levels in the EFS-stimulated corpus cavernosum were increased by amlodipine. Amlodipine did not affect the thiobarbituric acid-reacting substance levels in the serum and the corpus cavernosum, but did decrease superoxide dismutase activity in the tissue. Imidapril and hydralazine inhibited the acetylcholine-induced relaxation in the corpus cavernosum. Sodium nitroprusside-induced relaxation in the tissue was increased by amlodipine. All three agents similarly inhibited the phenylephrine-induced contraction. These results suggest that impaired neurogenic relaxation in the corpus cavernosum of SHR is improved by amlodipine and imidapril through an increase in the synthesis and/or release of neuronal NO, but not CO, and presumably the inhibited detumescence of erection, which is induced by norepinephrine being released from sympathetic neuron. These findings indicate that amlodipine and imidapril may ameliorate the decreased relaxation of cavernous smooth muscle in the setting of hypertension.
Ushiyama
Masayuki
M
Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
Kuramochi
Tomoya
T
Katayama
Shigehiro
S
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007202:Indicators and Reagents; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D007202:Indicators and Reagents; D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D014662:Vasoconstrictor Agents; D017311:Amlodipine; D010656:Phenylephrine; D009569:Nitric Oxide; D002248:Carbon Monoxide; D013482:Superoxide Dismutase; D006152:Cyclic GMP