The impact of cisplatin induced renal failure on baroreflex regulation of renal sympathetic nerve activity (RSNA) in the male Wistar rat

Renal failure (RF) in man is associated with sympatho-excitation. We investigated whether low and high pressure baroreceptor regulation of RSNA was deranged in a cisplatin-induced rat RF model. Rats received 5mg/kg cisplatin i.p. 7 days prior to study. Following anaesthesia (i.p. chloralose/urethane) baroreflex gain curves for RSNA were generated using a four parameter logistic regression equation and analysed for the level of impairment of RSNA. Control rats (n=8) had blood pressure (BP) of 100±1 mmHg and displayed a baroreflex RSNA curve with a sensitivity (slope, A2) of 0.16±0.01%/mmHg. RF rats (n=8) had BP of 96±1 mmHg and exhibited a significantly (P<0.05, Students unpaired t-test) blunted baroreflex curve with a sensitivity of 0.08±0.04 %/mmHg. During an acute volume expansion (i.v. saline 0.25% body weight/min for 30min) to challenge low-pressure barorecptors, control rats exhibited a reflex decrease in RSNA of some 70±6%, whereas it was unchanged in the RF group (3±2%). These data reveal a dys-regulation of both the low and high pressure baroreflex control of RSNA which could contribute to the hypertension associated with RF in man. Funding was from Health Research Board, Ireland.