Renal sympathetic denervation attenuates congestive heart failure in angiotensin II‐dependent hypertension: studies with Ren‐2 transgenic hypertensive rats with aorto‐caval fistula

Abstract

ObjectiveWe hypothesized that renal denervation (RDN) attenuates the progression of aorto‐caval fistula (ACF)‐induced heart failure (HF) and the development of renal dysfunction in Ren‐2 transgenic rats (TGR), a model of ANG II‐dependent hypertension.MethodsRDN (severing renal nerve fibers, followed by phenol application) was done one week after creation of ACF; the follow‐up period was 70 days. The animals studied were: 1) Sham‐operated TGR (initial n = 8); 2) Sham‐operated TGR + RDN (n = 9); 3) ACF TGR (n = 31); 4) ACF TGR + RDN (n = 34). In separate groups (n = 8 in each), three weeks after induction of ACF, renal artery blood flow (RBF, Transonic probe) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng).ResultsUntreated ACF TGR began to die 3 weeks after induction of ACF and the final survival rate was 10% (3 from 31). RDN substantially improved the final survival rate to 50% (17 from 34). Basal RBF was significantly lower in ACF TGR than in sham‐operated TGR (6.9 ± 0.4 vs. 10.1 ± 0.5 ml.min−1.g−1, p<0.05) and RDN did not alter it in any group. Both doses of ANG II decreased RBF more in ACF TGR than in sham‐operated TGR (−17 ± 2% vs. −9 ± 2% and −42 ± 3% vs. −25 ± 2%, p<0.05 in both cases) and RDN increased RBF responsiveness to ANG II in ACF TGR (to −29 ± 3% and to −74 ± 3%, p<0.05 in both cases) as well as in sham‐operated TGR (to −21 ± 3% and −42 ± 3%, p<0.05). Intrarenal NE comparably decreased RBF in ACF TGR and sham‐operated TGR, and RDN increased RBF responsiveness in both groups. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham‐operated TGR (+24 ± 2% vs. +11 ± 2% and +26 ± 2% vs. +13 ± 2%, p<0.05 in both cases) and RDN did not alter it in any group.ConclusionThe results show that RDN significantly improved survival rate in ACF TGR, however this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.Support or Funding InformationSupported by the Ministry of Health of the Czech Republic grant No. NV‐18‐02‐00053 awarded to L.Č. All rights reserved. Supported by MH CZ ‐ DRO („Institute for Clinical and Experimental Medicine – IKEM, IN 00023001“).