The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease

Yimin Yao, Cara M. Hildreth, Melissa M. Farnham, Manash Saha, Qi Jian Sun, Paul M. Pilowsky, Jacqueline K. Phillips*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: The effect of angiotensin II type I receptor (AT 1 R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined. Methods: Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O 2 in N 2 or 100% N 2 ventilation, 5% CO 2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT 1 R antagonist 3 mg/kg, intravenous). Results: Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but not lSNA, was reduced. Losartan reduced MAP in both strains and selectively improved baroreflex gain for sSNA (-1.2 ± 0.1 vs. -0.7 ± 0.07 %/mmHg; P < 0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in Lewis controls, but reduced or had no effect on these parameters, respectively, in LPK. The SNA response to somatosensory stimulation was biphasic, with latency to second peak less in LPK. Losartan ameliorated the depressor and sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK, but did not alter the central chemoreflex or somatosympathetic responses. Conclusion: Inhibition of the AT 1 R selectively improved baroreflex control of sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows in the LPK rat, suggesting these anomalies in reflex function are driven in part by angiotensin II.

Original languageEnglish
Pages (from-to)1249-1260
Number of pages12
JournalJournal of Hypertension
Volume33
Issue number6
DOIs
Publication statusPublished - 6 Jun 2015

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