The aim of this study was to investigate the impact of renal denervation on the blood pressure, plasma renalase content and expression of renalase and tyrosine hydroxylase (TH) in the kidney of spontaneous hypertensive (SH) rats and to explore the mechanism of renal denervation involved in lowering blood pressure. SH rats (n=48) were randomly assigned to baseline, surgery (renal denervation), sham and control groups. WKY rats matched in age (n=12) served as the baseline control group. All rats were housed until they were 12 weeks old. The rats in the baseline group and the WKY group rats were sacrificed, and blood and kidney were collected for examination. In the renal denervation, sham and control groups, the blood pressure was continuously monitored. One and six weeks after renal denervation, 6 rats in each group were sacrificed, and blood and kidney were collected for examination. ELISA was employed to measure the plasma renalase, and western blot analysis was performed to detect the expression of TH and renalase in the kidney. Compared with the WKY rats, SH rats in the baseline group had significantly increased blood pressure and markedly elevated TH protein expression (P<0.05), but dramatically reduced plasma renalase content and protein expression of renalase in the kidney (P<0.05). One week after surgery, the mean arterial pressure and TH protein expression in the surgery group was lowered compared with the baseline group and dramatically reduced when compared with the sham and control groups (P<0.05). In the surgery group, renalase levels were markedly increased compared with the baseline, sham and control groups (P<0.05). Six weeks after renal denervation, the mean arterial pressure and TH levels in the surgery group were significantly increased while the renalase content and expression were markedly reduced compared with those at week 1, however, there were no marked differences among the surgery, sham and control groups (P>0.05). Moreover, no pronounced differences in the above variables were found between the sham and control groups at any timepoint (P>0.05). Renal denervation can lower blood pressure, which may be attributed to the suppression of sympathetic nerves, increase in plasma renalase content and renalase expression in the kidney.
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.
Apple Valsa canker (AVC) weakens apple trees and significantly reduces apple production in China and other East Asian countries. Thus far, very few AVC-targeting biocontrol resources have been described. Here, we present a thorough description of a fungal isolate (Chaetomium globosum, 61239) that has strong antagonistic action toward the AVC causal agent Cytospora mali. Potato dextrose broth (PDB) culture filtrate of strain 61239 completely suppresses the mycelial growth of C. mali on PDA, and strongly constrained the development of AVC lesions in in vitro infection assays. UPLC and HPLC-MS/MS investigations supported that strain 61239 produces Chaetoglobosin A, an antimicrobial metabolite that inhibits C. mali. Using genome sequencing, we discovered a gene cluster in strain 61239 that may be responsible for chaetoglobosin A production. Two of the cluster's genes – cheA, a PKS-NRPS hybrid enzyme, and cheB, an enoyl reductase – were individually silenced, which significantly decreased chaetoglobosin A accumulation as well as the strain’s antagonistic activity against C. mali. Together, the findings of our investigation illustrate the potential use of Ch. globosum for the management of AVC disease and emphasize the significant contribution of chaetoglobosin A to the antagonistic action of strain 61239.
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