Icariin improves erectile function in spontaneously hypertensive rats by downregulating GRK2 in penile cavernous tissue.

Abstract

Background: Hypertension is an independent risk factor for erectile dysfunction (ED). Icariin can improve erectile function of spontaneous hypertensive rats (SHRs). GRK2 is closely related to the phosphorylation of eNOS and endothelial function.

Aim: To explore whether icariin can improve erectile function in SHRs by regulating the expression of GRK2 in penile cavernous tissue.

Methods: Eight-week-old WKY and SHR rats were randomly divided into four groups (n = 6 per group) as follows: WKY, WKY + icariin, SHR and SHR + icariin. The WKY + icariin and SHR + icariin groups were treated with 10 mg/kg/day icariin. After 4 weeks, the ICPmax/mean arterial pressure (MAP), serum testosterone, the levels of GRK2, p-AKT/AKT, p-eNOS/eNOS, and caspase-3; the protein interaction between GRK2 and AKT; the levels of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA); and the level of apoptosis in rat penile cavernous tissue were measured.

Outcome: The expression of GRK2 in penile cavernous tissue of SHR was significantly higher than that in WKY rats, resulting in the inhibition of the AKT/eNOS/NO pathway, increased levels of oxidative stress and apoptosis, and the impairment of erectile function.

Results: The ICPmax/MAP ratio in the SHR group was significantly lower than those in WKY and SHR + icariin groups (P < .01). In the SHR + icariin group, the expression levels of GRK2 and caspase-3, the interaction between GRK2 and AKT, the level of MDA and the rate of apoptosis in the penile cavernous tissue were significantly lower, and the levels of p-AKT and p-eNOS, the p-AKT/AKT and p-eNOS/eNOS ratios, and NO and SOD were significantly greater than those in the SHR group (P < .01).

Clinical implications: Icariin may improve the erectile function of hypertension by downregulating GRK2 expression in penile cavernous tissue.

Strengths and limitations: The specific mechanism via which icariin downregulates GRK2 needs to be further elucidated.

Conclusion: Icariin downregulates the expression of GRK2 in the penile cavernous tissue of SHRs, upregulates the AKT/eNOS/NO pathway, decreases oxidative stress and apoptosis, and ultimately improves erectile function.