The role of growth factor on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in the rats

Nitric oxide synthase (NOS) containing nerve regeneration can be seen six m onths after unilateral cavernous nerve neurotomy in rats. However its molec ular mechanism is still unknown. It is believed that growth factors are inv olved in this phenomenon. In this study we investigated the change of NOS c ontaining nerve fibers and the RNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha , TGF-beta(1), TGF-beta(2). TGF-beta(3) and NOS on the penis after cavernou s nerve neurotomy in rats. Male rats were divided into three groups: (1) sham operation (N=10); (2) un ilateral neurotomy of a 5 mm segment of the cavernous nerve (N=15); and (3) bilateral neurotomy (n=15). Electrostimulation of the intact cavernous ner ve or pelvic ganglion was performed at one, three and six months. Nicotinam ide adenine dinucleotide phosphate (NADPH) diaphorase staining was used to identify NOS in the penile nerve fibers. The gene expression for growth fac tors and bNOS was investigated in corporal tissue by reverse transcriptase- polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. One month after neurotomy, both unilateral and bilateral neurotomy groups s howed a significant decrease in NOS-containing nerve fibers on the dorsal a nd intracavernosal nerves on the side of neurotomy, and a significantly low er mRNA expression of bNOS, IGF-I and TGF-beta(2). At three months, the num ber of NOS-containing nerve fibers in the unilateral neurotomy group increa sed only slightly but at six months those in the intracavernosal nerve incr eased in a significant amount (P < 0.0001), however mRNA expression of bNOS , IGF-I and TGF-beta(2) showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dor sal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvi c ganglion stimulation. In the unilateral neurotomy group at six months, mo re NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regener ation derives from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater ma ximal intracavernosal pressure and a shorter latency period at six months t han at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta(2) may play a key role in regene ration of NOS-containing nerve fibers in the dorsal and intracavernosal ner ves after unilateral cavernous nerve injury.