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

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.