Protective Effects of Inhibition of Angiotensin II Type 1 Receptors in Cardiorenal Syndrome Type 1

Background: Connections between the heart and the kidneys have been recognized in ancient times from Avicenna’s Canon of Medicine, 1025 AD emphasizing the importance of maintaining their balance for overall health and well-being to Egyptian ‘Book of the Dead’ and the Old testament.However, by the mid-20th century when cardiac and renal functions were measurable, it was noted thatnsome patients with heart failure (HF) had impaired estimated renal glomerular filtration rates (eGFR). Since then, several potential pathways responsible for this cardiorenal connection have been investigated but mechanisms of heart-kidney interaction are still unclear, and there is nonspecific or effective therapy for CRS-1 and its prevention. Methods: Rats were randomized into 3 groups: Control, myocardial infarction group preteratment with losartan (4 mg/kg ×12) (MI+LOS) daily 7 days before and treament 7 days after MI.& MI with no LOS treatment. MI was induced by the ligation of the left coronary artery . At 3 weeks post-MI, animals were examined for hemodynamic functions including left ventricle systolic pressure (LVSP), aortic systolic (AS) pressure, LV diastolic pressure(LVDP), LV hypertrophy (LVH), and LV function. Hearts and kidneys were analyzed for antioxidant enzyme activities including superoxide dismutase, glutathione peroxidase, catalase and oxidative stress. After sacrificing the animals, the renal cortex and the heart were removed for histology. Results: At 3 wks post MI significant decrease in LVSP was associated with increased renal and myocardial lipid peroxidation to 67%, and 53% respectively. In MI group there was a decrease in antioxidants enzymes activities in the kidney including catalase (47%), glutathione peroxidase (37%) and superoxide dismutase (57%). In the MI+ LOS group pretreatment with losartan improved hemodynamic function and decreased oxidative stress in the kidney to 52% compared with MI group.(p-value less than 0.05). Conclusion: In CRS type 1 pretreatment with LOS mitigates congestive heart failure and AKI which correlates with a decrease in antioxidants and increase in oxidative stress in the heart and the kidney. This study suggests the role of angiotensin II type 1 (AT1) receptor blocker in the prevention of CRS. Elucidation of the complex pathophysiology of heart-kidney interaction is essential and the key to discovering novel preventive and therapeutic approaches in CRS-1,