Aim: To identify if inhibition of peripheral chemoreceptors influence respiratory sympathetic modulation and blood pressure in an animal model of chronic kidney disease (CKD). Background: Peripheral chemoreceptor hypersensitivity is believed to contribute to sympathetic overactivity in hypertension associated with various diseases including CKD. One mechanism by which this may occur is through enhanced respiratory sympathetic modulation, whereby respiratory activity amplifies nerve activity (SNA). Inhibition of peripheral chemoreceptor input could reduce this respiratory sympathetic modulation and therefore blood pressure in CKD. Methods: Experiments were performed in anaesthetised, vagotomised, paralysed and ventilated hypertensive Lewis Polycystic Kidney (LPK) and normotensive control Lewis rats (n = 6-8/strain). Blood pressure, phrenic nerve activity (PNA) and splanchnic SNA (sSNA) were measured in animals that had undergone bilateral CSN surgical denervation to inhibit peripheral chemoreceptor input to the brain. For technical reasons, only blood pressure of these animals could be measured before CSN denervation. Results: LPK rats were hypertensive before CSN denervation (LPK: 136±5 vs Lewis: 90±5mmHg; p<0.0001). Following CSN denervation, when compared to Lewis control rats, LPK rats showed higher sSNA (LPK: 5.9±0.6 vs Lewis: 3.4±0.3 μv; p<0.01) and larger respiratory related SNA (area under the curve in PNA triggered average of SNA: LPK: 5.09±1.4 vs Lewis: 2.5±0.4 μvxs; P<0.05). Blood pressure was normalised by CSN denervation in the LPK (LPK: 108±4 vs Lewis: 94±8 mmHg; p=0.24). Conclusions: Our findings suggest that while removal of peripheral chemoreceptor input can normalize blood pressure in the LPK model of CKD, it does not mediate this effect through a normalisation of respiratory sympathetic modulation. Inhibition of peripheral chemoreceptors may be a therapeutic target for CKD however the mechanism remains to be determined.
|Number of pages||1|
|Publication status||Published - Sep 2017|
|Event||53rd Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology - Darwin Convention Centre, Darwin, Australia|
Duration: 4 Sep 2017 → 6 Sep 2017