Respiratory sympathetic coupling in chronic kidney disease

Chronic kidney disease (CKD) is a major public health problem, resulting in significant morbidity and mortality. Among the different causes and comorbidities of CKD, hypertension draws special attention as it is often difficult to treat and increases cardiovascular risk in these patients. It has been established that sympathetic nerve activity (SNA) is increased in hypertension and CKD. Recent works suggest that respiratory modulation of SNA [respiratory sympathetic coupling (respSNA); the coordination between breathing and SNA] is a driving factor behind increased SNA in a number of diseased states including hypertension; however, the pattern of respSNA with its role in underlying mechanism in CKD is not yet known. Accordingly, the aims of the thesis were to (i) determine if respSNA is altered in a classical rat model of CKD, the Lewis Polycystic Kidney (LPK) rat and determine if this is associated with hypersensitivity of peripheral chemoreceptors; (ii) identify if the pattern of respSNA along with its association with peripheral chemoreceptors is different between male and female animals with CKD; (iii) examine if respSNA contributes to baroreflex dysfunction in CKD and (iv) to investigate if bilateral carotid sinus (CSN) transection, a method by which to prevent peripheral chemoreceptors input, results in reduction of respSNA and blood pressure in the LPK rat. The main finding was that the male LPK rats had amplified respSNA compared to Lewis control rats since very early age (5 weeks). Notably, peripheral chemoreceptor stimulation revealed more enhanced respSNA in both juvenile and adult LPK rats. The female LPK rats also exhibited amplified respSNA compared to female Lewis rats. Another significant finding was that inhibition of altered respSNA selectively improved the baroreflex response of SNA in LPK rats. Furthermore, transection of CSN decreased blood pressure in the LPK model of CKD, although respSNA was elevated in LPK rats that had undergone CSN transection compared to controls. The results help us to understand the basic linking between SNA and respiration, with the goal of targeting peripheral chemoreceptors and respSNA for novel therapies for hypertension associated with CKD.