Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats

Nathalia Juocys Dias Moreira,Leandro Eziquiel De Souza,Maikon Barbosa Da Silva,Daniela Farah,Gisele Silvério Lincevicius,Edson Dias Moreira,Ivana Cinthya Moraes-Silva,Fernando Dos Santos,Elia Garcia Caldini,Maria Cláudia Costa Irigoyen

doi:10.1038/s41598-020-78674-8

Abstract

Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. We assessed urinary volume, autonomic control and aorta vascular reactivity after acute RDN. Male normotensive Wistar rats and spontaneously hypertensive rats (SHR) were divided into normotensive + RDN (ND) or sham surgery (NS), and hypertensive + RDN (HD) or sham surgery (HS). Metabolic parameters and hemodynamic measurements were recorded 72h and 4 days after intervention, respectively. Aortic rings were studied 7 days post RDN in an isometric myograph. Concentration–response curves to phenylephrine, sodium nitroprusside and acetylcholine (10–10–10−5 M) were performed. Two-way ANOVA was used for group comparisons and differences reported when p < 0.05. Results are presented as mean ± SEM. Urinary volume was 112% higher in HD vs. HS (HS = 14.94 ± 2.5 mL; HD = 31.69 ± 2.2 mL) and remained unchanged in normotensive rats. Systolic BP was lower in HD rats (HS = 201 ± 12 vs. HD = 172 ± 3 mmHg) without changes in normotensive group. HD group showed increased HF and LF modulation (HS = 5.8 ± 0.7 ms2vs. HD = 13.4 ± 1.4 ms2; HS = 3.5 ± 0.7 ms2vs. HD = 10.5 ± 1.7 ms2, respectively). RDN normalized vascular reactivity in HD rats and increased phenylephrine response in ND rats. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may also have contributed to functional changes of the aorta.

Highlights

Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood
Renal denervation was not able to normalize spontaneously hypertensive rats (SHR) rats blood pressure, hypertensive denervated rats showed lower systolic and diastolic pressures when compared to hypertensive sham group (HS = 201 ± 12 mmHg vs. hypertensive + RDN (HD) = 172 ± 3 mmHg, and HS = 147 ± 8 mmHg vs. HD = 114 ± 4 mmHg, respectively), resulting in a lower mean pressure (HS = 175 ± 9 mmHg vs. HD = 141 ± 4 mmHg)
RDN did not change heart rate (HR) in normotensive Wistar or hypertensive rats, heart rate variance (HRVar) was higher in hypertensive rats when denervated (HS = 76 ± 9 ms[2] vs. HD = 208 ± 8 ms2), while no difference was observed in Wistar rats (NS = 115 ± 10 ms[2] vs. normotensive + RDN (ND) = 108 ± 12 ms[2], Fig. 2a and b)

Summary

Introduction

Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may have contributed to functional changes of the aorta. We have previously demonstrated the key role of renal nerves in cardiovascular homeostasis in hypertension induced by aortic ligation; complete denervation of the ischemic kidney was able to attenuate hypertension, normalize the renin plasma activity and baroreceptor reflex of heart rate 10 days after aortic ligation[6]. The more recent studies, with improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have presented positive outcomes (change in 24-h blood pressure at 2, 3 and 6 months)[10,11,12,13]. The beneficial effects of this technique on hypertension have been associated with mechanisms such as a progressive decrease in renin release and renal sodium retention[15] and attenuation of oxidative stress and inflammation[16]

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