Responsiveness of afferent renal nerve units in renovascular hypertension in rats

Abstract

Previous data suggest that renal afferent nerve activity is increased in hypertension exerting sympathoexcitatory effects. Hence, we wanted to test the hypothesis that in renovascular hypertension, the activity of dorsal root ganglion (DRG) neurons with afferent projections from the kidneys is augmented depending on the degree of intrarenal inflammation. For comparison, a nonhypertensive model of mesangioproliferative nephritis was investigated. Renovascular hypertension (2-kidney, 1-clip [2K1C]) was induced by unilateral clipping of the left renal artery and mesangioproliferative glomerulonephritis (anti-Thy1.1) by IV injection of a 1.75-mg/kg BW OX-7 antibody. Neuronal labeling (dicarbocyanine dye [DiI]) in all rats allowed identification of renal afferent dorsal root ganglion (DRG) neurons. A current clamp was used to characterize neurons as tonic (sustained action potential [AP] firing) or phasic (1–4 AP) upon stimulation by current injection. All kidneys were investigated using standard morphological techniques. DRG neurons exhibited less often tonic response if in vivo axonal input from clipped kidneys was received (30.4% vs. 61.2% control, p < 0.05). However, if the nerves to the left clipped kidneys were cut 7 days prior to investigation, the number of tonic renal neurons completely recovered to well above control levels. Interestingly, electrophysiological properties of neurons that had in vivo axons from the right non-clipped kidneys were not distinguishable from controls. Renal DRG neurons from nephritic rats also showed less often tonic activity upon current injection (43.4% vs. 64.8% control, p < 0.05). Putative sympathoexcitatory and impaired sympathoinhibitory renal afferent nerve fibers probably contribute to increased sympathetic activity in 2K1C hypertension.

Myocardial infarction with a preserved ejection fraction—the impaired function of the cardio-renal baroreflex

“…In accordance with our assumptions, we could demonstrate for the first time that in samples of first neurons from the nodose ganglia, a separation in tonic and phasic neurons existed as frequently described for neurons of respective dorsal root ganglia in the afferent renal pathway (Rodionova et al, 2021a;Rodionova et al, 2020a).…”

“…Afferent renal nerve activity, which is involved in the control of efferent sympathetic nerve activity ( Johns et al, 2011 ), was again decreased in myocardial infarction as described for nephritic rats, supporting our concept that a loss of the sympathoinhibitory control provided by afferent renal nerve pathways, rather than sympathoexcitatory effects of afferent renal nerve activity, occurred ( Rodionova et al, 2020b ). We have described a SP-dependent neurogenic mechanism of sympathoinhibition that evidently subserved tonically sympathoinhibitory afferent pathways ( Rodionova et al, 2021a ). Rats on a high-salt diet developed hypertension when renal afferent nerve pathways were interrupted by a dorsal rhizotomy, suggesting that afferent nerve fibers prevent the development of high blood pressure and increase sympathetic activity ( Kopp et al, 2003 ).…”

Effects of intrarenal pelvic infusion of tumour necrosis factor-α and interleukin 1-β on reno-renal reflexes in anaesthetised rats

“…Renal ischaemia induces the production of inflammatory mediators including TNF-α [83] which has been shown to enhance the sensitivity of sensory neurones at the DRG [84]. This also fits into the context of an impaired sympatho-inhibitory renal afferent nerve mechanism leading to increased sympathetic activity and hypertension in the 2K1C model [85] where high levels of TNF-α are reported in the kidney. Although the above findings point towards an interaction at the level of the renal pelvic receptors between TNF-α and adenosine, the role of other mechanisms such as the central processing mechanism of afferent nerve signals should not be excluded.…”

Afferent neurons of the kidney with impaired firing pattern in inflammation – role of sodium currents?

“…In the study of the afferent renal innervation in rat models, we use an in vitro model allowing for the investigation of dorsal root ganglion (DRG) neurons that originally had renal afferent nerve projections in vivo [ 9 , 10 , 21 , 22 ] since single afferent renal nerve bundles are delicate and difficult to investigate in vivo.…”

“…With the help of this model, DRG neurons can be categorized by their firing pattern as “tonic” (high activity) or “phasic” (low activity) [ 9 , 10 , 21 , 22 ]: Neurons that show sustained action potential (AP) generation during depolarizing current injection are defined as tonic neurons . In contrast, neurons showing only initial and transient AP generation during current injection were defined as phasic neurons .…”