Another study compared the response of surgically and medically castrated rabbits to vardenafil with that of control rabbits.  Castrated rabbits did not respond to vardenafil, whereas noncastrated rabbits did respond appropriately. This result suggests that a minimum amount of testosterone is necessary for PDE5 inhibitors to produce an erection.
The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. 
Men who do not respond or tolerate oral medications are best treated with an internal penile pump (IPP) commonly known as an inflatable implant. The Internal Penile Pump is an inflatable, water-filled device. During the course of a 45-minute outpatient procedure, the pump is inserted through a one-inch opening in the scrotal sac. By squeezing the pump, (which is contained completely within the scrotum), for approximately a minute, fluid is pumped into the penis, resulting in a long lasting erection. To return the penis to its flaccid state, simply press and hold down the pump. Once inserted, there is no maintenance required for the pump, which can remain in place for a lifetime. Couples are once again able to have spontaneous sex. Normal sensation including orgasm and ejaculation are not affected.
Oral PDE5i remains the first line treatment for NED from SCI. Three of the four PDE5i currently available in the U.S., avanafil excluded, have been investigated in the SCI, and all of the more recent studies have shown improvements in erectile function based on IIEF score compared to placebo when included (59-63). Other studies have also shown significant improvements in the IIEF score when compared to baseline (64-69). Furthermore, treatment efficacy when compared to placebo occurs despite LOI or American Spinal Injury Association (ASIA) score characterizing impairment related to the injury (59,61).
For best results, men with ED take these pills about an hour or two before having sex. The drugs require normal nerve function to the penis. PDE5 inhibitors improve on normal erectile responses helping blood flow into the penis. Use these drugs as directed. About 7 out of 10 men do well and have better erections. Response rates are lower for Diabetics and cancer patients.