Losartan normalizes peripheral chemoreflex control of sympathetic nerve activity in chronic kidney disease

Background: Impaired peripheral chemoreflex sensitivity has been suggested to contribute to sympathetic overdrive and hypertension in chronic kidney disease (CKD). The role of the renin-angiotensin system (RAS) in generating the sympathetic responses to activation of the peripheral chemoreflex in CKD remains unknown. Aim: To determine whether the peripheral chemoreflex function is affected by an acute inhibition of RAS in CKD using the Lewis polycystic kidney (LPK) rat model of CKD. Methods: Under urethane anesthesia (1.3 g/kg. i.p.), 12 week-old male LPK or Lewis control rats (n=8–10) were vagotomized, paralysed and artificially ventilated. Baseline values of arterial pressure (AP), renal (rSNA), lumbar (lSNA) and/or splanchnic (sSNA) sympathetic nerve activity were recorded. The peripheral chemoreflex was activated by ventilating the animal with 100% N2 inhalation for 12 seconds. The reflex was then repeated after administration of the RAS inhibitor losartan (3 mg/kg, i.v.). Results: Baseline values of AP (82±2 vs 93±4 mmHg), rSNA (3.1±0.6 vs 8.5±1.6 μV), lSNA (2.3±0.4 vs 6.9±1.6 μV) and sSNA (3.7±0.7 vs 6.6±1.2 μV) were all significantly higher in the LPK (P