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Updated: May 31, 2026
Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits
Published on: June 2, 2019
Internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction
Kyan J Allahdadi1, Johanna L Hannan, Adviye Ergul
1Department of Physiology, Georgia Health Sciences University, Augusta, GA 30912, USA. kyan_allahdadi@hotmail.com
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.
