Oxidative Stress in the Pathophysiology of Cardiorenal Syndrome Due to Pulmonary Hypertension Without Heart Failure

Background: Nearly one-fourth of patients with pulmonary hypertension (PH) present with concurrent acute kidney injury (AKI) that is associated with increased risk of death. However, hardly any data is available regarding the pathophysiology of AKI in PH particularly without right heart dysfunction. The objective of this study was in a preclinical model of CRS secondary to pulmonary hypertension to invesigate role of oxidative stress in the lung- kidney pathophysiological cross talk. Methods: Rats were randomized in two groups: (1) chemically induced pulmonary hypertension with no direct effect in the kidneyn or (2) Control. We evaluated PH with serial doppler echo for 1 wk via Pulmonary Artery Acceleration (PAAT), right ventricular systolic pressure (RVSP ), right ventricular end diastolic pressure (RVEDP) , ejection fraction (EF) & RV hypertrophy (RVH). At 1 wk the heart & the kidney tissue and plasma were used to analyze antioxidant enzymes; superoxide dismutase (SOD),nglutathione peroxidase (GSHPx) and lipid peroxidation to assess oxidative stress. After sacrificing animals, hearts and kidneys were removed for histopathology. To assess congestion, pieces of tissue from the lung, kidney and the RV were removed to obtain the wet/dry weight ratio. Results: At 1 week, in CRS group doppler Echo demonstrated a decrease in (PAAT) an indication of pulmonary hypertension, increase RVSP to 37% as well as RVEDP to 73% with no RVF & normal EF. Oxidative stress in lung , kidney and RV was associated with significant decrease in antioxidant enzyme activities of SOD and GSHPx. Light and electron microscopy of the Kidney showed ATN. Wet/dry weight showed mild congestion in the lung but not in the kidney and the heart. Conclusion: This is a novel experimental model of CRS due to pulmonary hypertension with RV pressure overload and without RV dysfunction. Increase oxidative stress in the lungs and the kidneys suggest a role for oxidative stress in complex pathophysiology of lung-heart-kidney interactions that is important in discovering novel therapeutic and preventive approaches in CRS due to pulmpnary hypertension.