Introduction: Normal lower urinary tract (LUT) function is dependent on the coordination between bladder and urethra, which is sensitive to a host of disorders, including diabetes mellitus (DM). Although STZ-induced diabetic rat model has been extensively used as a rodent model of the LUT dysfunction, it’s not a good physiological condition for diabetic patients. Our purpose is therefore to establish a physiological DM animal model with low dose insulin treatment, and examine the effects of L-arginine on urethral function in this animal model.
Methods: Thirty female Sprague-Dawley rats were divided into three groups. DM was initially induced by i. p. injection of STZ (65 mg/kg), and then received subcutaneous implantation of insulin under the mid dorsal skin. Isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were performed under urethane anesthesia. L-arginine (100 mg/kg), was administered intravenously. Subsequently, N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg/kg) was injected intravenously to inhibit NO synthase activity. The changes of urethral function among different groups in vitro were tested by organ bath.
Results: In vivo study, UPP nadir was only decreased by L-arginine both in Normal control (NC) and insulin-treated DM groups, but inhibited by L-NAME in all the groups (Fig.1). Furthermore, 5 out of 6 DM rats showed a similar detrusor-sphincter dyssynergia pattern after L-NAME (Fig.1). In vitro study, the ratio, namely urethral relaxation difference divided by relaxation before L-NAME administration, was significantly decreased in DM group (Fig.2).
Conclusions: Low dose insulin can protest against diuresis-induced bladder overdistention and increase urethral relaxation, and this may be attributed to the protection of NO synthase and urethral NO sensitivity, but the longer effects should be further explored. Source of