Time-dependent Changes in Erectile Function and Responsiveness to Phosphodiesterase Type 5 Inhibitor in Streptozotocin-induced Diabetic Rats

Cho, Sung Yong; Kim, Soo Woong

Abstract

PURPOSE
The aim of this study was to investigate time-dependent changes in erectile function and responsiveness to type 5 phosphodiesterase (PDE5) inhibitor in streptozotocin-induced diabetic rats.
MATERIALS AND METHODS
Seventy-five 8-week-old male Sprague-Dawley rats were randomly divided into two groups: diabetic (n=50) and control (n=25). The diabetic group received a single intraperitoneal injection of streptozotocin. The diabetic rats and age-matched control rats underwent cavernosometry before and after administration of DA-8159 (a novel PDE5 inhibitor) at 6, 8, 10, 12, and 14 weeks after induction of diabetes. The erectile response elicited by electrical stimulation of the cavernous nerve (3 V, width 0.2 msec, duration 30 seconds) was measured at several frequencies (2.5, 5, 10, and 20 Hz). Intracavernous pressure (ICP) and mean arterial pressure (MAP) were continuously monitored. Comparisons were made for ICP/MAP and areas under the curve (AUC) corresponding to the duration of electrical stimulation. The AUC was also corrected by the MAP.
RESULTS
Diabetic rats maintained normal erectile responses until 6 weeks after diabetic induction. Following 8 weeks of diabetes, the rats showed significantly lower ICP/MAP and AUC/MAP at higher frequencies of nerve stimulation, which were normalized to controls by administration of DA-8159. In contrast, both physiologic parameters were significantly decreased in the 10-week diabetic rats and ICP/MAP at 20 Hz stimulation frequency recovered only by injection of DA-8159. At more than 12 weeks of diabetes, the rats demonstrated severe deterioration of erectile function, which did not fully respond to PDE5 inhibitor.
CONCLUSIONS
Findings from this study indicate that impairment of erectile function is followed by decreased responsiveness to PDE5 inhibitor during the course of diabetes.