Time-dependent changes of erectile function in diabetic rats: role of systemic endothelial dysfunction

Abstract

Purpose: To understand the potential contribution of systemic endothelial dysfunction to diabetic erectile dysfunction, and the time course of erectile dysfunction in a streptozotocin (STZ)-induced diabetic rat model.

Materials and methods: Among 84, 12-week-old Sprague-Dawley rats, 48 rats received intraperitoneal STZ and were classified into six groups of diabetes by the period of observation (n=8). The remaining 36 rats were also grouped, similar to the diabetic groups, and served as normal controls. After 4, 6, 8, 10, 12, and 14 weeks of diabetes (serum glucose >250 mg%), all rats underwent cavernous nerve electrostimulation (3 V, 0.2 ms, 30 sec) with varying frequency (2.5~20 Hz). At the end of the study, 8 ml of blood was taken to measure the plasma markers of endothelial function and glycosylated hemoglobin.

Results: Compared to the control, significant reduction of erectile response was not observed until eight weeks after diabetes induction. The diabetic rats had elevation of all plasma markers except for l-selectin. However, the correlation analysis revealed that no systemic marker of endothelial dysfunction was associated with change in erectile function. Only the level of hemoglobin A1c (HbA1c) showed a modest but significant correlation with the peak intracavernosal pressure, corrected by mean arterial pressure (ρ=-0.183), and the area under the curve of the cavernosometry (ρ=-0.207).

Conclusions: Significant reduction of erectile function was not observed until eight weeks after the induction of diabetes. Except for HbA1c, there was no systemic marker associated with endothelial activation and erectile function in the diabetic rats.

Keywords: Diabetes mellitus; Endothelium; Erectile dysfunction; Rats.

Fig. 1

The effect of diabetes on body weight and serum glucose concentrations. (A) The rats were weighed at regular intervals for 14 weeks. (B) Blood glucose was measured every 2 weeks. Significant elevation of blood glucose was noted within 2 weeks of streptozotocin injection. ▪: nondiabetic control animals, ▴: streptozotocin-induced diabetic rats. ^*Statistically significant difference from control group at each point in time (p<0.05).

Fig. 2

Serial comparison of plasma markers between control and diabetic rats. The levels were measured after the tested rats were euthanized and blood was collected. (A) Intracellular adhesion molecule (ICAM), (B) e-selectin, (C) l-selectin, (D) von Willebrand factor, (E) high sensitivity C-reactive protein (hsCRP), (F) endothelin-1 and (G) hemoglobin A1c (HbA1c). ^*Statistically significant difference from control group at each point in time (p<0.05).