(429) Hypertension Impairs Erectile Function In SHR By Suppressing the Adiponectin/PI3K/AKT/eNOS Signaling Pathway

Introduction The mechanism by which hypertension causes ED is not clear. Objective To investigate whether hypertension impairs erectile function in rats via regulating the PI3K/AKT/eNOS pathway in penile corpus cavernosum, and the mechanism by which icariin improves erectile function in spontaneously hypertensive rats (SHR). Methods 12-week-old male WKY rats (WKY) and SHR were randomly divided into six experimental groups (n=6 per group) as follow, respectively. WKY group, WKY + icariin group, SHR group, SHR + icariin group, SHR + empty vector group, and SHR + adenovirus vector carrying adiponectin gene transfection group. The WKY + icariin and SHR + icariin groups were treated with 10 mg/kg/day icariin for 4 weeks. The ICPmax/mean arterialpressure (MAP), serum testosterone, the levels of adiponectin, PI3K, AKT, p-AKT, eNOS, and p-eNOS;and the levels of nitric oxide (NO) in rat penile cavernous tissue were measured. Results Compared to the WKY group, SHR rats exhibited significantly lower levels of NO and ICPmax/MAP in the penile corpus cavernosum. Adiponectin was predominantly expressed in the endothelial cells of the penile corpus cavernosum. The expression of adiponectin, as well as the levels of PI3K, p-AKT/AKT, and p-eNOS/eNOS, were markedly reduced in the SHR group compare to in the WKY group. Both the SHR + icariin group and the SHR + adenovirus vector carrying adiponectin gene transfection group showed significantly higher NO content and ICPmax/MAP compared to the SHR group (P < 0.05). Similarly, the expression of adiponectin and the ratios of PI3K, p-AKT/AKT, and p-eNOS/eNOS were significantly elevated in the SHR + icariin and SHR + adenovirus vector carrying adiponectin gene transfection groups compare to the SHR (P < 0.05). Conclusions Hypertension contributes to erectile dysfunction (ED) by downregulating the expression of adiponectin in penile endothelial cells, which subsequently inhibits the PI3K/AKT/eNOS signaling pathway. Treatment with icariin or adenovirus vector carrying adiponectin gene transfection effectively upregulates the expression of adiponectin in the penile endothelium of SHR, activates the PI3K/AKT/eNOS signaling cascade, and thereby improves erectile function. Disclosure No