IntroductionIn a renal disease model (anti‐Thy 1.1 nephropathy) the responsiveness of afferent renal nerve units was shifted from units with highly active primary neurons (tonic response pattern) to units with neurons of very low activity upon stimulation (phasic response pattern). Afferent renal nerve activity was likely decreased. Likewise, afferent vagal nerve activity in congestive heart failure had a lower frequency at saturation than controls. Hence we wanted to test the hypothesis that in congestive heart failure (CHF) the vagal afferent nerve pathway consists of a decreased number of highly active tonic sensory neurons in the nodose ganglion as compared to controls.Material and MethodsCHF was induced by coronary artery ligature, nephropathy by injections of an anti Thy1.1 antibody (OX7, 1.2mg/kg). After a respective time (CHF 21 days, nephropathy 7 days after induction) nodose ganglion neurons with cardiac vagal afferents from CHF rats or neurons form dorsal root ganglia with renal afferents from rats with nephropathy (as well as controls) were cultured. Current clamp was used to characterize neurons as “tonic”, i.e. sustained action potential (AP) firing or “phasic”, i.e. <5 APs upon current injection. Electrophysiological parameters and AP properties were determined in neurons from animals with CHF or nephropathy and compared to controls.ResultsMore than 100 neurons were investigated. In CHF rats, the number of neurons with a tonic, more active response pattern from CHF animals did not differ from controls (64% vs. 70 %, ns). However, tonic cardiac neurons from CHF rats exhibited an increased production of action potentials compared to controls (24.4+/−5.0 vs. 14.7+/−1.8 APs/10s; p<0.05; mean+/− SEM). In nephropathic rats, the number of neurons with a tonic, more active response pattern decreased significantly (43% vs. 64 %, p<0.05) as compared to controls, but there was no difference in action potential production between nephropathic rats and controls.ConclusionIn contrast to our hypothesis, in congestive heart failure the number of afferent neurons with a tonic response pattern was not significantly altered. However, the action potential production of these neurons even significantly increased upon stimulation. Hence, in congestive heart failure vagal afferent neurons increase their sensitivity in the presence of impaired intracardiac receptors whereas in renal disease the responsiveness of the first part of the afferent pathway is impaired as a whole.Support or Funding InformationDFG, German Research Foundation Interdisciplinary Center for Clinical Research ‐ University of Erlangen, Erlangen, GermanyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Objective: Afferent nerve pathways form kidney and heart are said to control sympathetic renal nerve activity. In a renal disease model the responsiveness of afferent renal nerve units was shifted from units with highly active primary neurons (tonic response pattern) to units with neurons of very low activity upon stimulation (phasic response pattern). Afferent renal nerve activity was likely decreased. Likewise, afferent vagal nerve activity in congestive heart failure (CHF) had a lower frequency at saturation than controls. Hence we wanted to test the hypothesis that CHF the vagal afferent nerve pathway consists of a decreased number of highly active tonic sensory neurons in the nodose ganglion. Design and method: CHF was induced by coronary artery ligature, nephropathy by injections of an anti Thy1.1 antibody (OX7, 1.2 mg/kg). After a respective time (CHF 21 days, nephropathy 7 days after induction) nodose ganglion neurons with cardiac vagal afferents from CHF rats or neurons form dorsal root ganglia with renal afferents from rats with nephropathy were cultured. Current clamp was used to characterize neurons as tonic, i.e. sustained action potential (AP) firing or phasict, i.e. <5 APs upon current injection. More than 100 neurons were investigated. Results: In CHF rats, the number of neurons with a tonic response pattern did not differ from controls (64% vs. 70 %, ns). However, tonic cardiac neurons from CHF rats exhibited an increased production of action potentials compared (24.4+/-5.0 vs. 14.7+/-1.8 APs/10 s; p < 0.05; mean+/-SEM). In nephropathic rats, the number of neurons with a tonic response pattern decreased significantly (43% vs. 64 %, p < 0.05), but there was no difference in action potential production between groups. Conclusions: In congestive heart failure the number of afferent neurons with a tonic response pattern was not significantly altered. However, the action potential production of these neurons even significantly increased upon stimulation. Hence, in congestive heart failure vagal afferent neurons increase their sensitivity in the presence of impaired intracardiac receptors whereas in renal disease the responsiveness of the first part of the afferent pathway is impaired as a whole.

Introduction: In experimental myocardial infarction with reduced ejection fraction causing overt congestive heart failure, the control of renal sympathetic nerve activity (RSNA) by the cardio-renal baroreflex was impaired. The afferent vagal nerve activity under these experimental conditions had a lower frequency at saturation than that in controls. Hence, by investigating respective first neurons in the nodose ganglion (NG), we wanted to test the hypothesis that after myocardial infarction with still-preserved ejection fraction, the cardiac afferent nerve pathway is also already impaired.Material and methods: A myocardial infarction was induced by coronary artery ligature. After 21 days, nodose ganglion neurons with cardiac afferents from rats with myocardial infarction were cultured. A current clamp was used to characterize neurons as “tonic,” i.e., sustained action potential (AP) firing, or “phasic,” i.e., &lt;5 APs upon current injection. Cardiac ejection fraction was measured using echocardiography; RSNA was recorded to evaluate the sensitivity of the cardiopulmonary baroreflex. Renal and cardiac histology was studied for inflammation and fibrosis markers.Results: A total of 192 neurons were investigated. In rats, after myocardial infarction, the number of neurons with a tonic response pattern increased compared to that in the controls (infarction vs. control: 78.6% vs. 48.5%; z-test, *p &lt; 0.05), with augmented production of APs (23.7 ± 2.86 vs. 15.5 ± 1.86 APs/600 ms; mean ± SEM, t-test, *p &lt; 0.05). The baseline activity of RSNA was subtly increased, and its control by the cardiopulmonary baroreflex was impaired following myocardial infarction: the fibrosis marker collagen I augmented in the renal interstitium.Discussion: After myocardial infarction with still-preserved ejection fraction, a complex impairment of the afferent limb of the cardio-renal baroreflex caused dysregulation of renal sympathetic nerve activity with signs of renal fibrosis.