Neurogenic erectile dysfunction: the course of nicotinamide adenine dinucleotide phosphate diaphorase-positive nerve fibers on the surface of the prostate.

OBJECTIVES: Nitric oxide (NO) plays an important role as a neurotransmitter in the peripheral neural regulation of erection. A histochemical stain able to localize fibers releasing NO in combination with an in vivo study were used to evaluate the course and physiologic significance of the nerve fibers innervating the cavernous smooth muscle. METHODS: Morphologic studies in 6 rats and 6 human cadavers were performed, tracing the course of branches of the cavernous nerve branches using a nicotinamide adenine dinucleotide phosphate diaphorase staining technique. Electrostimulations in rats were performed before and after transection of the anterolateral part of the prostate capsule. RESULTS: Multiple nerve fibers were documented running on the lateral and ventral surfaces of the prostate distinct from the classically described dorsolateral neurovascular bundle. Transection of these fibers resulted in a loss of electrically induced intracavernous pressure (59.4 +/- 5.6 cm H2O versus 27.0 +/- 4.6 cm H2O). CONCLUSIONS: These preliminary morphologic and physiologic studies support a significant role for these nerve fibers in erection.

7-Nitroindazole: a selective inhibitor of penile erection: an in vivo study in a rat animal model.

OBJECTIVES: The neuronal isoform of nitric oxide synthase (nNOS) has been localized in neurons innervating the penis and is believed to be an important mediator of erection. Using the selective inhibitor 7-nitroindazole (7-NI), we evaluated the possible role of nNOS in penile erection using a rat animal model. METHODS: Eighteen Sprague-Dawley rats were divided into three study groups. A sham group (n = 6) received the vehicle arachis oil, a low-dose group received 5 mg/kg (n = 6), and a high-dose group received 50 mg/kg (n = 6) of 7-NI prior to measurement of blood pressure and cavernous nerve stimulation-induced rise in intracavernous pressure. RESULTS: A dose-dependent inhibition of erection by 7-NI was seen. Control animals had an intracavernous pressure rise of 55.5 +/- 4.0 cm H2O, whereas the low-dose group had 26.5 +/- 2.8 cm H2O and the high-dose group had 6.2 +/- 2.1 cm H2O. A partial recovery of erection was seen in the low- and high-dose groups after 3 hours. Blood pressure was unaffected by 7-NI administration. CONCLUSIONS: 7-NI induced a reversible, dose-dependent inhibition of erection without affecting blood pressure. This in vivo study provides further evidence of the role played by nNOS in erection.

Evaluation of a no-needle penile injector: a preliminary study evaluating tissue penetration and its hemodynamic consequences in the rat.

OBJECTIVES: Intracavernous needle injection is an effective delivery method for pharmacotherapy of erectile dysfunction. Needle phobia, pain, and concern about local tissue injury have stimulated the search for new, less invasive means of inducing penile erection. In this preliminary communication, we evaluate a jet injector as an alternative to needle injection for intracavernous delivery of vasoactive drugs. METHODS: Jet injection was evaluated in three groups of rats receiving either India ink, saline, or papaverine into the penis. The ability of the jet injection to penetrate through the tunica albuginea and deliver liquid to the corpora cavernosa smooth muscle was assessed by the degree of staining within the corpus cavernosum (ink group), histologic change (saline group), and rise in intracavernous pressure (papaverine group). Erectile capacity following cavernous nerve electric stimulation was compared before and 1 hour after injection of saline or papaverine. RESULTS: Ink traversed the skin and tunica albuginea with extensive deposition noted within the cavernous spaces. Varying degree of subcutaneous hemorrhage were seen with saline jet injection; however, the corpus cavernous smooth muscles showed no evidence of injury. Jet injection of papaverine 3250 micrograms significantly increased cavernous pressure (39.4 +/- 4.6 cm H2O) compared with saline injection (2.8 +/- 1.3 cm H2O). CONCLUSIONS: We conclude that acute jet injection is an effective method for intracavernous delivery of drugs. Long-term effects should be evaluated prior to clinical use.

New insights into the role of endothelin-1 in radiation-associated impotence.

The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 microg/30 microl) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical field stimulation. In the 2000 cGy group, a significant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A significant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a significant improvement in erectile function following BQ-123 administration. A significant improvement was observed 20 min post-administration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals.