Different forms of afferent nerve input in cardiac and renal disease in rats?

Abstract

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.