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Effects of renal sympathetic denervation and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy

Comparison in spontaneously hypertensive rats

Auswirkungen der renalen Sympathikusdenervation und eines Angiotensin-converting-Enzym-Hemmers auf die linksventrikuläre Hypertrophie

Vergleich bei Ratten mit spontan aufgetretener Hypertonie

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Abstract

Objectives

The aim of this study was to investigate whether renal sympathetic denervation (RSD) is more effective on myocardial hypertrophy than the angiotensin-converting enzyme inhibitor (ACEI) perindopril in spontaneously hypertensive rats (SHRs).

Methods

After bilateral renal denervation blood pressure (BP) was measured every 10 days. On day 50 the heart was (histo)pathologically examined. The ventricular weight to body weight ratios (VW/BW), myocardial diameter and collagen volume fraction (CVF) were calculated, and cardiac hypertrophy marker genes were analyzed by RT-PCR.

Results

At the baseline evaluation all groups had comparable BP. After treatment the BP of the RSD group was significantly reduced (p < 0.05). The BP of the RSD group was lower than that of the perindopril group on days 10, 20 and 30th (p < 0.05) but on day 50 systolic BP of the RSD group was significantly higher (p < 0.05) whereas there were no significant differences in diastolic BP. The VW/BW decreased in the RSD group, whereas the value did not change significantly in the perindopril group. The myocardial diameter of the left ventricular cardiomyocytes was also significantly lower in the RSD group and stayed the same in the perindopril group. Collagen volume fraction (CVF) in the RSD group was significantly lower than in the perindopril group (p < 0.05). Significant changes in the expression levels of NPPA, MYH7, and MYH6 (P < 0.05) were observed in the RD-SHR groups (p < 0.05). There was a significant difference in the expression level of MYH6 (p < 0.05) between the RSD group and the perindopril group but the expression levels of NPPA and MYH7 were not significantly different.

Conclusion

In this study, RSD had a significant antihypertensive effect and inhibited hypertensive-induced cardiac hypertrophy in SHRs and showed advantages compared with ACEI in decreasing BP in the early stage and in inhibiting myocardial fibrosis.

Zusammenfassung

Ziel

Ziel der Studie war zu untersuchen, ob bei Ratten mit spontan aufgetretener Hypertonie (SHR) und Myokardhypertrophie die renale Sympathikusdenervation (RSD) wirksamer als der Angiotensin-converting-Enzym-Inhibitor (ACEI) Perindopril.

Methoden

Nach beidseitiger renaler Denervation wurde der Blutdruck (RR) alle 10 Tage gemessen. Am Tag 50 wurde das Herz histopathologisch untersucht. Das Verhältnis von Ventrikelgewicht zu Körpergewicht (VW/BW), Myokarddurchmesser und Kollagenvolumenfraktion (CVF) wurden ermittelt, Markergene für kardiale Hypertrophie wurden per Echtzeitpolymerasekettenreaktion (RT-PCR) analysiert.

Ergebnisse

Bei der Eingangsuntersuchung wiesen alle Gruppen einen vergleichbaren RR auf. Nach Therapie war der RR der RSD-Gruppe signifikant vermindert (p < 0,05). Der RR in der RSD-Gruppe war an Tag 10, 20 und 30 niedriger als in der Perindopril-Gruppe (p < 0,05), aber an Tag 50 war der systolische RR der RSD-Gruppe signifikant höher (p < 0,05), während es keine signifikanten Unterschiede beim diastolischen RR gab. Der VW/BW-Wert nahm in der RSD-Gruppe zwar ab, doch er änderte sich in der Perindopril-Gruppe nicht signifikant. Der anhand der linksventrikulären Kardiomyozyten bestimmte Myokarddurchmesser war in der RSD-Gruppe ebenfalls signifikant geringer und blieb in der Perindopril-Gruppe gleich. Die CVF war in der RSD-Gruppe signifikant niedriger als in der Perindopril-Gruppe (p < 0,05). Signifikante Veränderungen des Expressionsgrads von NPPA, MYH7 und MYH6 (p < 0,05) wurden in der RSD-SHR-Gruppe festgestellt (p < 0,05). Es bestand ein signifikanter Unterschied beim Expressionsgrad von MYH6 (p < 0,05) zwischen der RSD-Gruppe und der Perindopril-Gruppe, nicht jedoch beim Expressiongrad von NPPA und MYH7.

Schlussfolgerung

In dieser Studie hatte die RSD eine signifikante antihypertensive Wirkung, sie hemmte die hypertonieinduzierte kardiale Hypertrophie bei SHR und wies Vorteile im Vergleich zum ACEI bei der RR-Senkung im Frühstadium sowie bei der Hemmung der Myokardfibrose auf.

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Compliance with ethical guidelines

Conflict of interest. Xueyan Ding, Xudong Xu, Yan Yan, Xiaowei Song, Suxuan Liu, Guokun Wang, Dingfeng Su, Qing Jing, and Yongwen Qin state that there are no conflicts of interest. All national guidelines on the care and use of laboratory animals have been followed and the necessary approval was obtained from the relevant authorities.

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Authors and Affiliations

  1. Department of Cardiology, Changhai Hospital, 2nd Military Medical University, 168 Changhai Road, 200433, Shanghai, PR China

    X. Ding, X. Xu, X. Song, S. Liu, Q. Jing & Y. Qin

  2. Cardiovascular Therapeutic Centre, The 117 Hospital of the Chinese People’s Liberation Army, Hangzhou, Zhejiang, PR China

    X. Ding

  3. Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, PR China

    Y. Yan

  4. Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China

    G. Wang & Q. Jing

  5. School of Pharmacy, Second Military Medical University of China, Shanghai, PR China

    D. Su

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  1. X. Ding
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  7. D. Su
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  8. Q. Jing
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  9. Y. Qin
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Corresponding author

Correspondence to Y. Qin.

Additional information

Xueyan Ding and Xudong Xu contributed equally to this study..

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Ding, X., Xu, X., Yan, Y. et al. Effects of renal sympathetic denervation and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy. Herz 40, 695–701 (2015). https://doi.org/10.1007/s00059-014-4110-5

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  • DOI: https://doi.org/10.1007/s00059-014-4110-5

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