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

Abstract

The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (Po0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.

Effects of hyperglycemia on rat cavernous nerve axons: A functional and ultrastructural study

“…This same study, and a second (Yagihashi and Sima, 1986), also examined the DNP in STZ-treated rats and reported axonal shrinkage and axonal accumulations of glycogen. Abnormally dilated nerve fibers and engorged endings of autonomic nerves were described in rat penile shaft after 5–8 months of HG (Morrison et al, 2007a,b), corresponding to the time scale of severe neuropathy in our recordings. The lack of change in morphology of MPG and proximal CN, and limited abnormalities in distal segments of CN presented in our findings and previous histological evaluations, suggest the prevalence of functional, but not structural, HG-induced alterations in CN.…”

A critical appraisal of erectile function in animal models of diabetes mellitus

“…In a recent study using STZ diabetic rat, the CC displayed 350% NA concentration over control values at 8 weeks (Morrison et al. , 2007).…”

Increased peripherin in sympathetic axons innervating plantar metatarsal arteries in STZ-induced type I diabetic rats

“…However, whether this effect of STZ-induced diabetes involves an increase in the number of axons within the nerve fibers was not resolved. Other studies have indicated that STZ-induced diabetes stimulates growth of sympathetic nerve terminals in the heart (Felten et al, 1982), corpus cavernosum (Morrison et al, 2007), and seminal vesicle (Morrison et al, 2006). In both corpus cavernosum and seminal vesicle, the TH-IR of the nerve fibers was increased (Morrison et al, 2006, 2007).…”

“…Other studies have indicated that STZ-induced diabetes stimulates growth of sympathetic nerve terminals in the heart (Felten et al, 1982), corpus cavernosum (Morrison et al, 2007), and seminal vesicle (Morrison et al, 2006). In both corpus cavernosum and seminal vesicle, the TH-IR of the nerve fibers was increased (Morrison et al, 2006, 2007). In addition, STZ-induced diabetes increased the NPY content of both the corpus cavernosum and seminal vesicle (Morrison et al, 2009).…”

“…Therefore, the sympathetic neurons supplying the PMAs appear to be selectively vulnerable to the effects of type 1 diabetes. It has been reported that STZ-induced diabetes produces swelling of sympathetic axons supplying the intestine, corpus cavernosum and pineal gland (Schmidt et al, 1981; Morrison et al, 2007; Tsai et al, 2008). In mesenteric nerves supplying the distal ileum and colon of diabetic rats, Schmidt et al (Schmidt et al, 1981, 1988; Schmidt and Scharp, 1982; Clark and Schmidt, 1984) have described both degenerating and regenerating sympathetic axons.…”