Chronic intermittent hypobaric hypoxia prevents pulmonary arterial hypertension through maintaining eNOS homeostasis

Aims: Pulmonary arterial hypertension (PAH) is a pathological condition in which pulmonary artery pressure is elevated which causes patients to die of right heart failure. Chronic intermittent hypobaric hypoxia (CIHH) represents a novel method of intermittently exposing subjects to a simulated plateau hypobaric hypoxia environment. This study investigates the potential preventive and protective effects of CIHH on PAH. Main methods: Male Sprague-Dawley rats were randomly divided into four groups: control group (Con), chronic intermittent hypobaric hypoxia group (CIHH), pulmonary arterial hypertension group (PAH), chronic intermittent hypobaric hypoxia + pulmonary arterial hypertension group (CIHH + PAH). To evaluate the effects of CIHH on PAH, a range of techniques was employed, including pulmonary hemodynamics, vascular reactivity assay, Western blot, RNA sequencing, HE staining and co-immunoprecipitation. Key findings: CIHH was demonstrated to reduce pulmonary artery constriction and enhance relaxation, reducing the mean pulmonary artery pressure in PAH rats. This is achieved through attenuating the CaM/eNOS (Calmodulin,CaM)protein interaction and increasing the CaV1/eNOS (Caveolin-1,CaV1) protein interaction, thereby preventing eNOS overactivation contribution to improving NO bioavailability in PAH rats. Significance: CIHH prevents PAH by maintaining eNOS homeostasis in PAH rats.