CYCLOSPORINE A-INDUCED NEPHROTOXIC SPRAGUE-DAWLEY RATS ARE MORE SUSCEPTABLE TO ALTERED VASCULAR FUNCTION AND HAEMODYNAMICS

Cyclosporine A (CsA) is widely employed in the management of solid organ transplantation but often brought occurrence of nephrotoxicity. The present study investigates its potential deleterious effects on the cardiovascular and renal excretory function as well as on the renal haemodynamics. Male Sprague Dawley rats (n=16) were randomized into two groups viz. control (CT) and CsA treated group (CS). CS rats received CsA for 21 days at 25mg/kg/day p.o. Renal excretory functions were determined at day 0 and day 21 respectively. The vascular and renal heamodynamics were measured at the end of treatment period. Pulse pressure and pulse wave velocity was used as the markers of vascular stiffness. Data are presented as Mean±SEM and were analyzed by student’s t-test with significance at (p<0.05). CS rats showed significant (P<0.05) reduction in body weight (CT: 271±8 g; CS: 215±9 g) fluid intake (CT: 27±1 ml; CS: 24±1 ml), creatinine clearance (CT: 5.1±0.2 ml/min/kg; CS: 3.4±0.1 ml/min/kg), glomerular filtration rate (CT: 1.4±0.2 ml/min/kg; CS: 0.5±0.1 ml/min/kg), fractional excretion of sodium (CT: 0.7±0.1 %; CS: 0.1±0.0%) and fractional excretion of potassium (CT: 29.0±4.8 %; CS: 10.9±1.1 %) compared to CT rats. Systolic blood pressure (CT: 117±2 mmHg; CS: 145±1 mmHg) together with urinary protein excretion (CT: 25.8±1.9 mg/ml/kg; CS: 49.3±1.3 mg/ml/kg) were elevated (P<0.05) in CS rats. The baseline renal cortical blood perfusion (CT: 181±8 BPU; CS: 158±3 BPU) was blunted in CS group compared to CT group. Besides that, the pulse pressure (CT: 32±2 mmHg; CS: 38±1 mmHg) and pulse wave velocity (CT: 3.7±0.1 m/s; CS: 5.0±0.2 m/s) were observed slightly higher in CS group than CT group. The current study suggests that CsA induced renal failure rats experienced attenuation in renal cortical blood flow and high blood pressure. This was the consequence of the higher sympathetic and renin-angiotensin system activity. High index of pulse pressure and pulse wave velocity indicated that CsA treated rats were more susceptible to cardiovascular disorder than non CsA treated rats.