Pde5 Inhibition Reduced Blood Pressure and Alleviated Target Organ Damage in Chronic Intermittent Hypoxia

Abstract

The role of phosphodiesterase 5 (Pde5) in obstructive sleep apnea (OSA) induced damage remains unclear. Our study aimed to investigate the role of Pde5 in chronic intermittent hypoxia (CIH) model. C57BL/6J wild-type (WT) mice (n=48) and Pde5 knockout (Pde5-/-) mice (n=24) were randomly assigned to CIH group and room air (RA) group. After 6 weeks, some WT mice (n=24) in CIH group were given sildenafil or saline gavage for another 4 weeks. Blood pressure was regularly measured during the experiment. Echocardiography was used to estimate cardiac function. We collected organs from each group of mice and measured their physical indicators. Histochemical staining was used to explore the size of cardiomyocyte and fibrosis area of various organs. Cyclic guanosine monophosphate (cGMP) and Malondialdehyde (MDA) concentrations in serum were measured by ELISA assay. Compared to the RA-treated group, the 6-week CIH resulted in a significant increase in blood pressure, altered heart structure and reduced serum cGMP in WT mice. Pde5-/- mice and sildenafil intragastric administration significantly reduced systolic blood pressure in CIH condition and attenuated the damage of target organs. In CIH model, we found that the cardiomyocyte size and fibrosis area of heart and kidney significantly reduced in Pde5-/- groups. Besides, endogenous and exogenous inhibition of Pde5 reduced MDA level and inflammatory and oxidative stress markers expression in CIH condition. In the present study, we found that Pde5 inhibition could reduce blood pressure and alleviate target organ damage in the CIH model, which may be mediated through the oxidative stress pathway.