Restoration of Female Genital Vasocongestive Arousal Responses in Young and Aged Rats

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 (ETAR; 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. ETAR 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.

Section: Discussionsupporting

confidence: 91%

Internal Pudendal Artery from Type 2 Diabetic Female Rats Demonstrate Elevated Endothelin-1-Mediated Constriction

Allahdadi

Hannan

Ergul

et al. 2011

“…However, other studies have revealed that select antihypertensive treatments have improved erectile function in hypertensive rats and in humans [30–33]. In particular, drugs that antagonize the renin‐angiotensin system are associated with improved endothelial function, decreased type III collagen in corpora cavernosum and improved erectile function in hypertensive male rats and genital vasocongestive arousal responses in female rats [32,34–36]. Despite this functional evidence, the impact of these changes on the morphology of the pudendal artery, a key resistance vessel, remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Impact of Hypertension, Aging, and Antihypertensive Treatment on the Morphology of the Pudendal Artery

Hannan

Blaser

Pang

et al. 2011

Self Cite

Introduction Aging and hypertension increase the risk of erectile dysfunction (ED) and cardiovascular disease. Arterial insufficiency is likely a primary factor in hypertension-related ED. Given the dominance of internal pudendal arteries in controlling penile vascular resistance, pathological changes in this vessel would be critical for inducing ED in aged hypertensives. Aim We assessed the age-related impact of hypertension and its treatment on erectile function and pudendal artery structure in young and old spontaneously hypertensive rats (SHRs). Methods Erectile responses were monitored in 15- and 77-week-old SHR and Wistar Kyoto (WKY) rats using apomorphine (80 mg/kg). At sacrifice, the vasculature was perfusion-fixed and aorta, renal, mesenteric, and internal pudendal arteries assessed morphometrically using light and electron microscopy. A separate group of 15-week SHR were treated with enalapril and hydrochlorothiazide (30 mg/kg/day, 2 weeks) followed by 2 weeks off treatment, after which the same vessels were assessed morphometrically. Arterial pressures were determined using radiotelemetry. Main Outcomes Measured Erectile function, vessel morphology (lumen diameter, wall thickness, cross-sectional area, extracellular matrix [ECM]) and arterial pressure. Results Erectile responses were similar in young SHR and WKY (1.7 ± 0.80 vs. 1.4 ± 0.85) but declined significantly in aged SHR (0.3 ± 0.49). Vascular aging in SHR was associated with striking pudendal remodeling, characterized by marked neointimal proliferation and disruptions of the internal elastic lamina. This remodeling involved thickening of the medial layer (35 ± 6.0 µm vs. 81 ± 3.5 µm, P < 0.01), decreased lumen diameter (282 ± 6.3 µm vs. 250 ± 12.4 µm, P < 0.05) and increased ECM (10 ± 2.0 µm2 vs. 26 ± 10.6 µm2, P < 0.001). In old pudendals, there were significantly more round synthetic smooth muscle cells bordering the intima and in the neointima. Antihypertensive treatment decreased the wall : lumen ratio in young SHR pudendal arteries (−17%). Conclusions Vascular aging in SHR with ED involved distinctive pathogenic remodeling in the internal pudendal artery. In young SHR, brief antihypertensive therapy was able to regress this abnormal morphology.

“…Recently, female sexual dysfunction has attracted much interest in the field of medical sciences [2–10]. Female sexual dysfunction, which consists of multiple disorders, are categorized as hypoactive sexual desire disorder, orgasmic disorder, sexual arousal disorder, and sexual pain disorder [2,5,6,11–14]. Female sexual arousal disorder refers to a lack of responsiveness to sexual stimulation in women [15].…”

Section: Introductionmentioning

confidence: 99%

Extraction and Microencapsulation of Khat: Effects on Sexual Motivation and Estradiol Level in Female Rats

Aziz

Peh

Tan

2009

Introduction Khat (Catha edulis) is an evergreen tree/shrub that is thought to affect sexual motivation or libido. Its positive effect on sexual desire is more frequently observed in females than in males and occurs when khat is chewed. Thus, khat’s effects on sexual behavior may depend on the release mode of its active constituent. Aim This study aimed to investigate the effect of dried khat alkaloids on the sexual motivation and estradiol levels of female rats, with special emphasis on the importance of the sustained release effect. Methods Dried khat leaves were extracted and isolated. The alkaloids in khat extract were identified and calculated using thin layer chromatography and high-performance liquid chromatography. The isolated khat extract was microencapsulated using a phase separation coacervation method. The morphology, particle size, yield, drug loading, and entrapment efficiency were evaluated. The in vitro release and stability of alkaloids in khat extract and in khat extract microcapsules were determined. The effect of khat extract microcapsules and varying doses of khat extract on sexual motivation in female rats were investigated. Additionally, estradiol levels, vaginal secretions and vaginal pH were determined. Main Outcome Measures The differences in the effect of khat extract and khat extract microcapsules on sexual motivation, vaginal secretion and estradiol levels in female rats were compared. Results Cathine and norephedrine were identified in the isolated khat extract at composition of 81.3% and 17.2%, respectively. Among the formulations studied, khat extract microcapsules of formulation 2:3:5 (containing a ratio of khat extract to ovalbumin to gelatin of 2:3:5) were found to exhibit higher yield, loading, and entrapment efficiency. Khat extract microcapsules showed sustained in vitro release and were more stable than khat extract. In addition, khat extract microcapsules enhanced sexual motivation, increased vaginal secretions, and upregulated estradiol level in female rats. Conclusion The sustained release of alkaloids from dried khat has significantly enhanced the sexual motivation and increased the estradiol level of female rats. Thus the release of dried khat alkaloids from microcapsules might be an effective means of enhancing the libido in females.