Noradrenergic innervation of the penis in control and streptozotocin‐diabetic rats: Evidence of autonomic neuropathy

Abstract

The noradrenergic sympathetic innervation of the penis of control and 4-month streptozotocin-diabetic rats was examined with the glyoxylic acid histofluorescence method. Noradrenergic varicosities were found in the corpora cavernosa in a dense subtunical plexus and in the perisinusoidal and trabecular regions of the erectile tissue, in the corpus spongiosum in perisinusoidal tissue, around large arteries and veins, and around small tortuous arterioles and small draining veins of the corpora cavernosa and spongiosum. Noradrenergic varicosities were diminished in number and fluorescent intensity in all regions of the penis of diabetic rats compared with controls. The subtunical plexus was absent, perisinusoidal and trabecular varicosities were sparse, and only occasional intermittent, discontinuous, dull fluorescent fibers or plexuses were found around the vessels. Quantitation with high-performance liquid chromatography revealed a significant reduction of norepinephrine in the penis of diabetic rats compared with controls. The present study suggests that long-term streptozotocin diabetes in the rat is accompanied by sympathetic autonomic neuropathy of the penis that seems to parallel changes in the noradrenergic content of penile corpora of men with diabetes and erectile impotence. The streptozotocin-diabetic rat merits further study to explore the relationship between noradrenergic innervation of the penis and erectile tissue.

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

“…9 The vasoconstrictor neurotransmitter NA is also known to increase in concentration in a variety of tissues including the rat heart, tail artery and whole penis, [10][11][12] and the time course of these changes often involves a peak in concentration that can occur after several, or many months of hyperglycaemia. However, while some authors have found a reduction in the noradrenergic [13][14][15] and nitrergic 16,17 innervation in diabetic erectile tissue, the results on the noradrenergic nerves are not confirmed in a recent publication 12 and in the present work. Changes in the concentration of NA in the CC may or may not influence erectile function, depending on when and where there is an increased release, and indeed if there is a change in release at all, one might expect the inhibition of erection 18,19 and facilitation of detumescence.…”

“…The same group, however, in a different paper illustrating some of the variability of the responses, described either no change or an increase in varicosities at 4 month and 1 month, respectively. 14 Reasons for the discrepancy may be (a) the methodology, (b) Sprague-Dawley rats were used by Felten et al, 13 whereas Wistar rats were used in the present study; (c) Felten et al 14 used a larger dose of STZ at a younger age, and had evidence that there were differences in the response of the sympathetic nerves if diabetes was induced at a later age. Felten et al 13,14 also used rats which had a greater blood glucose level and excluded animals with a blood glucose of less than 300 mg/dl, and finally (d) they included the sub-tunical plexus where the sympathetic terminals are very densely packed.…”

“…14 Reasons for the discrepancy may be (a) the methodology, (b) Sprague-Dawley rats were used by Felten et al, 13 whereas Wistar rats were used in the present study; (c) Felten et al 14 used a larger dose of STZ at a younger age, and had evidence that there were differences in the response of the sympathetic nerves if diabetes was induced at a later age. Felten et al 13,14 also used rats which had a greater blood glucose level and excluded animals with a blood glucose of less than 300 mg/dl, and finally (d) they included the sub-tunical plexus where the sympathetic terminals are very densely packed. Other authors who have suggested that the autonomic nitrergic nerves to the CC of the rabbit clitoris degenerate in diabetics, have also used treatment regimes that induce a severe form of the diabetes.…”

“…Felten et al 13 studied the sympathetic innervation of the penis in STZ-diabetic rats 4 months after the onset of hyperglycaemia and found that the number of noradrenergic varicosities and the NA content of the CC were greatly reduced. They commented on the variability of the results in the diabetic animals but concluded that there was a reduction in visible sympathetic terminals (as indicated by the fluorescence technique), all of which is contrary to the present results, using tyrosine hydroxylase histochemistry.…”

Noradrenergic innervation of the superior mesenteric artery in streptozotocin-diabetic rats.

“…From these studies the existence of a localized (i.e. found in some organs and not in others) impairment of adrenergic, serotoninergic and peptidergic innervation was demonstrated in streptozotocin-treated animals (5,8,10,11,16) . On the contrary, information concerning the innervation pattern of blood vessels in diabetes is almost exclusively limited to studies of vascular reactivity after infusion or in vitro application of catecholamines (5).…”