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Long-term renal sympathetic denervation ameliorates renal fibrosis and delays the onset of hypertension in spontaneously hypertensive rats

This study was designed to explore the effects of long-term renal denervation (RDN) on blood pressure and renal function in spontaneously hypertensive rats (SHR). RDN was performed in bilateral renal arteries with 10% phenol in absolute ethanol in SHR and Wistar-Kyoto rats (WKY) at 13 weeks. Age-matched SHR and WKY served as controls. Blood pressure was measured. Plasma, urine and kidneys were collected 8 months after the RDN operation. Plasma renin activity (PRA), aldosterone levels, reactive oxidative stress, renal function and structural remodeling were assessed. RDN-treated SHR demonstrated a lower spontaneous rise in systolic blood pressure than rats in the SHR-Sham group (P < 0.01, at 20, 27, 34 and 41 weeks), except at 48 weeks (198.2 ± 12.9 vs 209.4 ± 11.9 mmHg, P = 0.145). WKY were not affected by RDN. Renal tissue norepinephrine was decreased by RDN in both SHR and WKY. Plasma PRA activity, aldosterone levels, and NAD(P)H oxidase activity were reduced by the RDN in SHR. Plasma eNOS and NO were increased by RDN only in SHR. The renal nerve was destroyed by RDN with no regeneration after 8 months. The progression of renal dysfunction associated with urinary protein excretion, glomerular sclerosis, and tubulointerstitial fibrosis was attenuated by RDN only in SHR through downregulation of the ACE/Ang II/AT1R axis and upregulation of the ACE2/Ang-(1-7)/MasR axis in the kidney. Thus, RDN delays the onset of hypertension and ameliorates glomerular sclerosis and tubulointerstitial fibrosis in SHR

Year of Publication: 2018
Contained in: American journal of translational research Vol. 10, No. 12 (2018), p. 4042-4053
All journal articles: Search for all articles in this journal
Language: English
Contributors: Wang, Ming | Author
Han, Wenzheng
Zhang, Min
Fang, Weiyi
Zhai, Xinrong
Guan, Shaofeng
Qu, Xinkai
Full text access:
Electronic availability is being checked...
Keywords: Journal Article
Renal sympathetic denervation
glomerular sclerosis
hypertension
renal fibrosis
ISSN: 1943-8141
Note: Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Notes: Date Revised 20.11.2019
published: Electronic-eCollection
Citation Status PubMed-not-MEDLINE
Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
PMID:
    30662649

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520 |a This study was designed to explore the effects of long-term renal denervation (RDN) on blood pressure and renal function in spontaneously hypertensive rats (SHR). RDN was performed in bilateral renal arteries with 10% phenol in absolute ethanol in SHR and Wistar-Kyoto rats (WKY) at 13 weeks. Age-matched SHR and WKY served as controls. Blood pressure was measured. Plasma, urine and kidneys were collected 8 months after the RDN operation. Plasma renin activity (PRA), aldosterone levels, reactive oxidative stress, renal function and structural remodeling were assessed. RDN-treated SHR demonstrated a lower spontaneous rise in systolic blood pressure than rats in the SHR-Sham group (P < 0.01, at 20, 27, 34 and 41 weeks), except at 48 weeks (198.2 ± 12.9 vs 209.4 ± 11.9 mmHg, P = 0.145). WKY were not affected by RDN. Renal tissue norepinephrine was decreased by RDN in both SHR and WKY. Plasma PRA activity, aldosterone levels, and NAD(P)H oxidase activity were reduced by the RDN in SHR. Plasma eNOS and NO were increased by RDN only in SHR. The renal nerve was destroyed by RDN with no regeneration after 8 months. The progression of renal dysfunction associated with urinary protein excretion, glomerular sclerosis, and tubulointerstitial fibrosis was attenuated by RDN only in SHR through downregulation of the ACE/Ang II/AT1R axis and upregulation of the ACE2/Ang-(1-7)/MasR axis in the kidney. Thus, RDN delays the onset of hypertension and ameliorates glomerular sclerosis and tubulointerstitial fibrosis in SHR 
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