2 型糖尿病雌性大鼠阴部内动脉表现出内皮素-1 介导的收缩增强。
Internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction.
机构信息
Department of Physiology, Georgia Health Sciences University, Augusta, GA 30912, USA.
出版信息
J Sex Med. 2011 Sep;8(9):2472-83. doi: 10.1111/j.1743-6109.2011.02375.x. Epub 2011 Jun 30.
INTRODUCTION
Diabetes is a risk factor for female sexual dysfunction (FSD). FSD has several etiologies, including a vasculogenic component that could be exacerbated in diabetes. The internal pudendal artery supplies blood to the vagina and clitoris and diabetes-associated functional abnormalities in this vascular bed may contribute to FSD.
AIM
The Goto-Kakizaki (GK) rat is a non-obese model of type 2 diabetes with elevated endothelin-1 (ET-1) activity. We hypothesize that female GK rats have diminished sexual responses and that the internal pudendal arteries demonstrate increased ET-1 constrictor sensitivity.
METHODS
Female Wistar and GK rats were used. Apomorphine (APO)-mediated genital vasocongestive arousal (GVA) was measured. Functional contraction (ET-1 and phenylephrine) and relaxation (acetylcholine, ACh) in the presence or absence of the ETA receptor antagonist (ETA R; atrasentan) or Rho-kinase inhibitor (Y-27632) were assessed in the internal pudendal and mesenteric arteries. Protein expression of ET-1 and RhoA/Rho-kinase signaling pathway was determined in the internal pudendal and mesenteric arteries.
MAIN OUTCOME MEASURE
APO-mediated GVAs; contraction and relaxation of internal pudendal and mesenteric arteries; ET-1/RhoA/Rho-kinase protein expression.
RESULTS
GK rats demonstrated no APO-induced GVAs. Internal pudendal arteries, but not mesenteric arteries, from GK rats exhibited greater contractile sensitivity to ET-1 compared with Wistar arteries. ETA R blockade reduced ET-1-mediated constriction in GK internal pudendal and mesenteric arteries. Rho-kinase inhibition reduced ET-1-mediated constriction of GK internal pudendal but not mesenteric arteries; however, it had no effect on arteries from Wistar rats. RhoA protein expression was elevated in GK internal pudendal arteries. At the highest concentrations, ACh-mediated relaxation was greater in the GK internal pudendal artery; however, no difference was observed in the mesenteric artery.
CONCLUSIONS
Female GK rats demonstrate decreased sexual responses that may be because of increased constrictor sensitivity to the ET-1/RhoA/Rho-kinase signaling in the internal pudendal artery.
简介
糖尿病是女性性功能障碍（FSD）的一个危险因素。FSD 有多种病因，包括血管生成成分，而糖尿病可使这种血管成分恶化。阴部内动脉为阴道和阴蒂供血，而糖尿病相关的血管床功能异常可能导致 FSD。
目的
Goto-Kakizaki（GK）大鼠是一种非肥胖型 2 型糖尿病模型，其内皮素-1（ET-1）活性升高。我们假设雌性 GK 大鼠的性反应减弱，阴部内动脉的 ET-1 收缩敏感性增加。
方法
使用雌性 Wistar 和 GK 大鼠。测量阿朴吗啡（APO）介导的生殖器血管充血性觉醒（GVA）。评估在存在或不存在 ETA 受体拮抗剂（atracentan）或 Rho 激酶抑制剂（Y-27632）的情况下，阴部内和肠系膜动脉的功能性收缩（ET-1 和苯肾上腺素）和舒张（乙酰胆碱，ACh）。在阴部内和肠系膜动脉中测定 ET-1 和 RhoA/Rho 激酶信号通路的蛋白表达。
主要观察指标
APO 介导的 GVAs；阴部内和肠系膜动脉的收缩和舒张；ET-1/RhoA/Rho 激酶蛋白表达。
结果
GK 大鼠没有 APO 诱导的 GVA。与 Wistar 动脉相比，来自 GK 大鼠的阴部内动脉，但不是肠系膜动脉，对 ET-1 的收缩敏感性更高。ETA R 阻断减少了 GK 阴部内和肠系膜动脉中 ET-1 介导的收缩。Rho 激酶抑制减少了 GK 阴部内动脉，但不减少肠系膜动脉中 ET-1 介导的收缩；然而，它对 Wistar 大鼠的动脉没有影响。GK 阴部内动脉中 RhoA 蛋白表达升高。在最高浓度时，GKA 内 pudendal 动脉的 ACh 介导的舒张更大；然而，在肠系膜动脉中没有观察到差异。
结论
雌性 GK 大鼠表现出性反应减弱，这可能是由于阴部内动脉中 ET-1/RhoA/Rho 激酶信号的收缩敏感性增加所致。
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