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

Abstract

Inhibition of the AT1R 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.

Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

“…We also sought to identify if altered sympathetic activity in the conscious LPK is associated with deficits in regulatory pathways known to impact autonomic neuroregulation of the cardiovascular system including the chemoreceptor reflex and behavioral stress. Tonic activation of excitatory chemoreceptor afferents has been proposed as a driver of elevated SNA in CKD patients (Hering et al, 2007 ; Despas et al, 2009 ) and we have recently shown under anesthetized conditions that the LPK animals have impaired peripheral and central chemoreflex responses (Yao et al, 2015 ). Accordingly, our second aim was to assess RSNA and blood pressure responses to central (hypercapnia) and peripheral (hypoxia) chemoreceptor stimulation in the conscious LPK.…”

“…Indirectly, hypotensive responses to ganglionic blockade (Phillips et al, 2007 ; Ameer et al, 2014 ), bradycardic responses to β 1 -adrenoceptor blockade (Harrison et al, 2010 ) and low-frequency power of systolic blood pressure variability (Harrison et al, 2010 ; Hildreth et al, 2013b ) are all increased in the LPK. Directly, we have recently shown that RSNA in anesthetized animals display elevated absolute baseline tonic levels (Salman et al, 2014 , 2015 ; Yao et al, 2015 ). Given the potential effect of anesthesia on SNA, which may be influenced to a greater degree in the disease state (Hildreth et al, 2013a ), a key objective of the present study was to record RSNA in conscious unrestrained animals using telemetry, examining the hypothesis that a sustained elevation in RSNA is a key pathological feature of CKD.…”

“…Elevated levels of muscle SNA features in many cardiovascular diseases and as a tool has provided an incredibly valuable snapshot into SNA at both the multiunit and single unit recording level in humans (Lambert et al, 2008 ) and has been used to assess for example the impact of renal denervation on muscle SNA in essential hypertension (Hering et al, 2013 ), however muscle SNA cannot provide mechanistic data as to what pattern of SNA is influencing visceral organs such as the kidney (Grassi et al, 2015 ) and it does not provide a long-term monitoring approach. Direct recordings of SNA to specific organ beds can be acquired from acute recordings in unconscious animals (Yao et al, 2015 ), however these may be unavoidably confounded by the effect of anesthetic on both SNA and blood pressure. Urethane anesthesia, for example, has been shown to both promote and inhibit SNA (Shimokawa et al, 1998 ; Wang et al, 2014 ) and altered baseline levels of blood pressure due to anesthetic will alter SNA through baroreflex mechanisms.…”

Glycinergic neurotransmission in the rostral ventrolateral medulla controls the time course of baroreflex‐mediated sympathoinhibition

“…The left renal sympathetic nerve was prepared and recorded using bipolar silver hook electrodes as described previously (Yao et al 2015). The activity was amplified (10,000×) and filtered (100-1000 Hz).…”

Cardiovascular Autonomic Dysfunction in Chronic Kidney Disease: a Comprehensive Review

“…Hypertension, which is present in~80-85 % of CKD patients [4,5], is a powerful indicator of CVD and an independent risk factor for disease progression both in adult and in pediatric patients with CKD [5,7]. Several mechanisms have been implicated in the pathogenesis of hypertension and CVD in CKD, including sodium retention and fluid overload due to defects in the pressure natriuresis relationship, activation of the renin-angiotensinaldosterone system (RAAS) [8,9,10•], sympathetic nervous system (SNS) hyperactivity [9, 11, 12••, 13••], autonomic dysfunction [13••, 14, 15], endogenous and environmental stress [5,16], impaired endothelial function, vascular remodeling, and arterial calcification [17,18], thus highlighting a complex interplay of neural, hormonal, and vascular mechanisms linking kidney disease to high blood pressure (BP) and the associated cardiovascular problems that consequently arise.…”