Objective
To examine the effects of the selective 5‐HT1A receptor agonist, NLX‐112, on urethral function in streptozotocin‐induced diabetic rats.
Materials and Methods
Female Sprague–Dawley rats (n = 32) were divided into two groups: rats with type 1 diabetes mellitus (T1DM) and age‐matched normal control rats (NC). T1DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Isovolumetric cystometry and urethral perfusion pressure (UPP) were evaluated 10 weeks postinjection in rats (n = 9 per group). The selective 5‐HT1A receptor antagonist, WAY‐100635 maleate salt, was administered after NLX‐112 hydrochloride dose–response curve was generated (intravenously). The remaining rats were used for immunofluorescence and Western blot assays.
Results
Compared to controls, type 1 diabetic rats (T1D rats) had lower maximal intravesical pressure (IP max) and UPP changes. In T1D rats, NLX‐112 hydrochloride (0.003–1.0 mg/kg) induced dose‐dependent decreases in UPP nadir, IP max, high‐frequency oscillations (HFOs) rate; and increases in UPP change and HFOs amplitude. WAY‐100635 maleate salt (0.3 mg/kg) partially or completely reversed the NLX‐112‐induced changes. Immunofluorescence revealed that 5‐HT1A receptors were found in the L6‐S1 spinal cord dorsolateral nucleus, but the expression was significantly higher in the T1D rats. Additionally, Western blot showed there were significantly more 5‐HT1A receptors in the ventral L6‐S1 spinal cord of T1D rats.
Conclusions
Urethral dysfunction in T1D rats was improved by NLX‐112. 5‐HT1A receptors were upregulated in the dorsolateral nucleus of L6‐S1 spinal cord in T1D rats. These findings suggest that NLX‐112 may constitute a novel therapeutic strategy to treat diabetic urethral dysfunction.