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RENAL DENERVATION IMPROVES RIGHT VENTRICULAR FUNCTION, RESTORES NOREPINEPHRINE LEVELS, AND REVERSES VENTRICULAR SPECIFICITY OF SELECTED MARKERS IN HYPERTENSIVE RATS WITH HEART FAILURE INDUCED BY VOLUME OVERLOAD

M. Miklovič, O. Gawryś, Z. Honetschlägerová, P. Kala, Z. Husková, S. Kikerlová, Z. Vaňourková, M. Adamová, H. Maxova, G. Puertas-Frias, A. Kvasilová, M. Kitamoto, Š. Jíchová, L. Steiner Mrázová, A. Vrbacká, V. Stránecký, T. Mráček, D. Sedmera, V. Melenovský (Prague)

Topic: Heart failure

Type: Presentation - doctors, CCVRID 2024

Aim
Despite the known antihypertensive effect of renal denervation (RDN), its influence on the
cardiac function, particularly of right ventricle (RV) and cardiac sympathetic nervous
system in heart failure (HF) is poorly understood. This study aimed to investigate the
effect of RDN on RV function, myocardial norepinephrine (NE), and left versus right
ventricular (LV/RV) dominance of HF markers in HF induced by aorto-caval fistula in rats (ACF).
Sample and Methodology
ACF was created in hypertensive Ren-2 transgenic rats. RDN was performed by phenol
application. RV and LV function was measured by echocardiography and pressure-volume
analysis. NE levels were measured using an ELISA kit, protein expression by
western blotting, gene expression by TaqMan PCR, RNA-seq by NovaSeq and ROS by Amplex Red assay.
Results
RDN in ACF rats decreased RV hypertrophy and dilatation, RV end-systolic (ESP) and end-diastolic pressure (EDP), improved RV systolic function, decreased HF gene markers Nppa, Collagen I/III ratio, Tgm2, Myh7/6 ratio, and increased SOD2 protein expression. RDN decreased plasmatic NE, increased NE in RV, and decreased monoamine oxidase (MAO-A) in RV. RDN downregulated most of profibrotic transcripts which ACF upregulated.
ACF changed ventricular specificity from LV to RV in Ees, EDPVR, and
molecular markers Mao-a, ROS production by MAO-A, Nppa, Myh7, Myh7/6 ratio, Tgm2,
Uchl1, and Beta1/Chrm2 ratio. Interestingly, RDN reversed ventricular specificity back towards LV in gene markers Mao-a,
Nppa, Myh7, Tgm2, Uchl1, and Beta1/Chrm2 ratio.
Conclusion
RDN decreased RV ESP and EDP, improved RV systolic function, restored NE levels, decreased expression of MAO-A, decreased RV gene expression of selected HF markers, and reversed their RV/LV dominance, probably by reduction of central sympathetic nerve drive and alternations of the cardiac sympathetic nervous system.