Hypertension up-regulates yes-associated protein expression in the penile corpus cavernosum and suppresses erectile function in spontaneously hypertensive rats.

INTRODUCTION

Hypertension is an important risk factor for erectile dysfunction. Yes-associated protein (YAP) is a multifunctional protein involved in diverse biological processes; whether hypertension influences erectile function through the regulation of YAP remains unclear; therefore, this study investigated whether hypertension impairs erectile function in spontaneously hypertensive rats (SHR) by upregulating YAP expression in the penile corpus cavernosum.

METHODS

Twelve 8-week-old male WKY rats were randomly divided into the WKY group and the WKY + LV group (n = 6), and twenty-four 8-week-old male SHR rats were randomly divided into four groups: the SHR group, SHR + NC group, SHR + LV group, and SHR + RES group (n = 6). SHR + RES group received resveratrol (10 mg/kg/d) by gavage for 4 weeks, and the WKY + LV,SHR + LV and SHR + NC groups were treated with a single intracavernosal injection of YAP siRNA lentivirus or empty vector (20 μL/rat, 1 × 109 TU/mL) at week 4. One week later, ICPmax/MAP, serum testosterone, NO, and expression of YAP, Caspase-1, Gasdermin D-N, Caspase-3, and p-eNOS/eNOS in the corpus cavernosum were measured.

RESULTS

YAP was predominantly expressed in the cytoplasm and nuclei of endothelial cells in the corpus cavernosum. Compared with the WKY group, the SHR group showed significantly lower NO levels, ICPmax/MAP, and p-eNOS/eNOS expression, but significantly higher expression of YAP, Caspase-1, GSDMD-N, and Caspase-3. In contrast, both the SHR + LV and SHR + RES groups showed significantly increased NO levels and ICPmax/MAP, decreased YAP, Caspase-1, GSDMD-N, and Caspase-3 expression, and reduced endothelial apoptosis and pyroptosis compared with the SHR group (P < .05).

DISCUSSION: Hypertension impairs erectile function by upregulating YAP expression in the penile corpus cavernosum, thereby promoting endothelial apoptosis and pyroptosis and reducing p-eNOS/eNOS and NO production, whereas resveratrol may ameliorate these changes by suppressing YAP expression.