Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms

Abstract

PURPOSE:To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-κB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were markedly higher than that in the WKY group (p<0.05). In the D1 and D2 group, the LVMI, NE and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were significantly reduced (p<0.05). CONCLUSION: Renal denervation can significantly delay the progression of left ventricular hypertrophy in spontaneously hypertensive rats, which may be attributed to the not only the suppression of sympathetic activity and attenuation of pressure load but the improvement of myocardial immuno-inflammation. Key words: Denervation. Kidney. Hypertrophy, Left Ventricular. Toll-Like Receptor 4. Ventricular Remodeling. Norepinephrine. Rats. RESUMO OBJETIVO:Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D) e grupo sham(S).12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI). RESULTADOS:No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-κB, TNF-α e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p<0,05). Nos grupos D1 e D2, o LVMI, NE e a expressão proteica de TLR4, NF-κB, TNF-α e IL-6 no miocárdio foi significantemente reduzido (p<0,05). CONCLUSÃO: A denervação renal pode significantemente retardar a progressão da hipertrofia ventricular esquerda em ratos espontaneamente hipertensos, o que pode ser atribuído não apenas pela supressão da atividade simpática e atenuação da pressão, mas pela melhora na imunoinflamação miocárdica.

Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine β-hydroxylase inhibition with etamicastat

“…Hypertension in SHR is a heterogeneous, multifactorial disorder. 46,47 In agreement with previous reports, [48][49][50] in this study, we showed that specific renal sympathetic nervous system ablation causes a transitory decrease in BP in SHR. Transient increases in NA levels were observed 7 days post RDN in the left ventricle of the heart and in the adrenal glands, which resulted in an increase, albeit not significant, in urinary NA levels (7 days), before returning to values similar to those in control SHR by the end of the assessment period.…”

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

“…Similarly, TLR4 plays a role in paraventricular nucleusmediated autonomic dysfunction in SHR (Dange et al, 2015) and in rats with angiotensin II-induced hypertension (Dange et al, 2014). Less is known about the contribution of TLR4 on hypertensive kidney dysfunction; however, renal denervation can significantly decrease myocardial TLR4 expression in SHR (Jiang et al, 2012), and angiotensin II upregulates TLR4 expression on mesangial cells (Wolf et al, 2006).…”

Renal denervation attenuates cardiac hypertrophy in spontaneously hypertensive rats via regulation of autophagy

“…Results of previous animal experiments also support the protective role of RD against LV hypertrophy. In a previous study with SHRs, Jiang et al found that RD can significantly delay the progression of left ventricular hypertrophy, possibly not only through the suppression of sympathetic activity and attenuation of pressure load, but also due to the reduction in myocardial inflammation, as reflected by significantly reduced myocardial levels of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrotic factor alpha (TNF-α) and interleukin 6 (IL-6) after RD ( 22 , 31 ). In a subsequent study in hypertensive type 1 diabetic rats, Thaung et al found that bilateral RD reduces cardiac hypertrophic remodeling in these rats without restoring the attenuated cardiac β-AR responsiveness ( 32 ).…”

“…These observations have been confirmed in subsequent clinical studies ( 18 – 20 ). Interestingly, some animal studies also found similar benefits of RD on cardiac hypertrophy and cardiac remodeling in various animal models ( 21 – 23 ), Mechanisms aside from attenuation of blood pressure and reduction in the activity of sympathetic nerves have been proposed to account for these changes, including a reduction in myocardial inflammation ( 22 ). However, whether RD has the ability to attenuate cardiac hypertrophy, induced by pressure overload of the LV, remains to be confirmed, and the potential mechanisms by which this may occur are not currently known.…”