期刊
JOURNAL OF NEUROTRAUMA
卷 37, 期 6, 页码 868-876出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2019.6676
关键词
cystometry; defecation; neurokinin 2 agonist; spinal cord injury; voiding
资金
- National Institutes of Health through an National Institute of Neurological Disorders and Stroke grant [NS089880]
- NCI [2-P30-CA016086-40]
- National Institute of Environmental Health Sciences [2-P30ES010126-15A1]
- University of Cancer Research Fund
- National Carolina Biotechnology Center [2015-IDG-1007]
Acute administration of [Lys5,Me,Leu9,Nle10]-NKA(4-10) (LMN-NKA) produces contractions of the detrusor and rectum with voiding in intact and acutely spinal cord injured (SCI) rats. In the current study, the ability of LMN-NKA (10 mu g/kg or 100 mu g/kg, subcutaneous [SC], twice a day [bid]) or vehicle to induce voiding and defecation in chronic SCI rats was examined across 30 days. After the last day of administration, voiding response rates and bladder pressure (BP) responses to LMN-NKA (intravenous [IV] and SC) were evaluated under anesthesia. In conscious rats, LMN-NKA (100 mu g/kg) produced dose-dependent micturition within 5 min, with response rates >90%, and voiding efficiency >80% in males and >60% in females, which remained stable across the 1-month test period. Similarly, LMN-NKA administration rapidly induced defecation, which also remained stable. Under anesthesia, LMN-NKA increased BP, voiding efficiency, and voiding response rates, which reached 100% at 3 and 10 mu g/kg IV in males and females, respectively. SC administration produced 100% response rates in males (30 mu g/kg) but only 71% in females (100 mu g/kg). Efficacy in rats chronically treated with LMN-NKA was similar to naive and vehicle-treated rats, except for reduced voiding efficiency in chronically dosed female rats (100 mu g/kg). No differences in bladder weights or collagen-to-smooth muscle ratios in histological sections were seen between the groups. Thus neither tolerance, nor sensitization, to LMN-NKA-induced micturition and defecation occurs with chronic administration in rats with chronic SCI. Efficacy was higher in male than in female rats.
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