P-20/BO-03 : Dysregulated miR-25, -99, -155, -451 and Renin Angiotensin System in High salt diet – induced Cardiac dysfunction of uninephrectomized rats

posted Jan 26, 2017, 6:32 AM by sourav ghosh

Venkateswara Rao Amara, Sunil Kumar Surapaneni, Kulbhushan Tikoo
National Institute of Pharmaceutical Education and Research (NIPER) S.A.S. Nagar, Mohali, India

Background & rationale: Uninephrectomy is not associated with major adverse cardiovascular or renal events both preclinically and clinically. Due to modernisation, excursion in food habits such as increased intake of salt, fructose, sucrose, carbohydrates, fats, etc. is seen at alarming rate. The deleterious effects of high salt intake are well known in normal (binephric) condition, but that of in the live kidney donors is largely unknown. Hence, the present study was undertaken to get an insight into the development and progression of cardiac dysfunction in uninephrectomized rats fed with high salt diet.
Methods: Studies conducted so far started high salt diet immediately after uninephrectomy surgery, which is least likely to occur in clinical scenario. In order to exactly mimic the clinical situation, we fed the uninephrectomized rats initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt diet (10% w/w NaCl). Kidney function tests (albumin, urea and creatinine), cardiovascular functions (SBP, DBP, HR, LVSP, LVEDP, +dP/dt, -dP/dt, baroreflex sensitivity) were measured at the end and histological, molecular studies (western blotting and RT-qPCR) were carried out after sacrifice.
Results: Uninephrectomized rats fed with high salt diet exhibited renal and cardiovascular dysfunction manifested in the form of decreased baroreflex sensitivity, increased in vivo cardiovascular reactivity to angiotensin II. Cardiac dysfunction is associated with decreased SERCA, AMPK and increased AKT and corresponding alteration in the miRNA (miR-25, -451, -99b, -155) regulating the expression of these proteins. The pattern of circulating miRNAs is opposite to that of the tissue miRs.
Conclusion: This study gives a preliminary idea on the cardiovascular and renal function of live kidney donors consuming high salt diet. Since the levels of tissue and circulating miRs do not match with each other, caution must be exercised in harnessing their role as diagnostic and prognostic markers.