Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat

Abstract

The rapid spread of locally restricted neural and hormonal signals among the vast array of largely inexcitable corporal smooth muscle cells is an absolute prerequisite to normal erectile function. And yet the mechanism(s) responsible for this phenomenon is not well understood. As a first step toward a more integrative understanding of erectile physiology and/or dysfunction, an 8- to 12-wk period of experimental diabetes was induced in 2-mo-old male Fischer 344 rats by either intraperitoneal streptozotocin (STZ) injection (35 mg/kg; n = 22) or subtotal pancreatectomy (n = 11). Fourteen age-matched control animals received injection of vehicle only while nine others served as sham-operated control animals. Eight STZ-diabetic animals received insulin replacement. Erectile function was assessed by evaluation of penile reflexes and monitoring of intracavernous pressure responses to both electrical stimulation of the cavernous nerve and intracorporal papaverine or nitroglycerin injection. Intracavernous pressure responses to neurostimulation were significantly attenuated in both STZ-diabetic and subtotal pancreatectomy animals compared with age-matched control animals (P < 0.05). Penile reflexes were also significantly diminished (P < 0.05). Regression analysis revealed that diabetes-related decreases in neurostimulated intracavernous pressure responses were strongly correlated with diminished synaptophysin immunoreactivity in the corpora (P < 0.001; r = 0.88). However, there were no detectable diabetes-related differences in pharmacological erections induced by intracavernous papaverine or nitroglycerin injection. Northern analysis revealed a marked diabetes-related increase in the amount of connexin 43 mRNA measured in frozen corporal tissue. Insulin replacement partially restored (attenuated the loss of) synaptophysin immunoreactivity and maintained neurostimulated intracavernous pressure responses to control levels while having no effect on penile reflexes. These observations may have important implications to the understanding of erectile physiology as well as the etiology of diabetes-related erectile dysfunction.

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats

“…These procedures have been described previously. 22,23 All procedures were performed in accordance with the NIH regulations and rats were maintained under controlled temperature and lighting.…”

“…These procedures have been described previously. 18,23 The Tulane University School of Medicine Animal Care and Use Committee has approved all procedures used in the present study.…”

Hypercontractility and impaired sildenafil relaxations in the BKCachannel deletion model of erectile dysfunction

“…smooth muscle; calcium-activated potassium channel; mouse ERECTILE DYSFUNCTION (ED) is described as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance (44). It affects 30 million men in the United States (5), and its prevalence increases with age and diseases like diabetes and hypertension (4,24,31). Erectile function and a proper penile erection occurs in response to nerve stimulation and the release of nitric oxide (NO) from parasympathetic nonadrenergic-noncholinergic (NANC) nerves as well as from the vascular endothelium (2,13,16,27).…”

Diabetes-induced changes in specific lipid molecular species in rat myocardium

“…This dose of streptozotocin has been demonstrated to produce moderate diabetes with impaired glucose-induced insulin secretion similar to subtotal pancreatectomy [22]. Diabetic animals did not gain as much weight over 6 weeks (375p25 g at the baseline and 384p35 g after 6 weeks, n l 12) as age-matched control animals (408p26 g at the baseline and 494p36 g after 6 weeks, n l 5) but otherwise remained in good health.…”