Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction
Background: Sodium-dependent glucose transporter-2 inhibitors (SGLT-2i) have potential hypotensive effects, enhancing the hypotensive effect of renal denervation (RDN). Spontaneously hypertensive rats (SHRs) were used to verify this hypothesis and explore the associated underlying...
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IMR Press
2025-06-01
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| author | Hao Zhang Zhuqing Li Wei Cai Yanxin Wang Jiaxin Feng Xuemei Yin Qi Li Ning Yang Chengzhi Lu Yuming Li |
| author_facet | Hao Zhang Zhuqing Li Wei Cai Yanxin Wang Jiaxin Feng Xuemei Yin Qi Li Ning Yang Chengzhi Lu Yuming Li |
| author_sort | Hao Zhang |
| collection | DOAJ |
| description | Background: Sodium-dependent glucose transporter-2 inhibitors (SGLT-2i) have potential hypotensive effects, enhancing the hypotensive effect of renal denervation (RDN). Spontaneously hypertensive rats (SHRs) were used to verify this hypothesis and explore the associated underlying pathways. Methods: Seven Wistar-Kyoto (WKY) rats and 35 SHRs were divided into 6 groups. The blank WKY control (W) group consisted of all 7 WKY rats, whereas the SHRs were divided into the following groups, each containing 7 rats: sham operation (Sham), renal denervation (RDN), SGLT-2 inhibitor treatment (SGLT-2i), and the combination of renal denervation with SGLT-2 inhibitor treatment (RDN+SGLT-2i). The rats in the RDN+SGLT-2i and SGLT-2i groups were gavaged with dapagliflozin (DAPA) before RDN. The sham group was subjected to a sham operation. One-week post-operation, rat tail manometry, and echocardiography were subsequently performed, and peripheral blood inflammatory cells were detected via flow cytometry before sample collection. Following sample collection, the serum, including interleukin-6, angiotensin-II, renin, and norepinephrine, was tested via enzyme-linked immunosorbent assay. Pathological testing included Masson staining of the myocardial tissue, tyrosine hydroxylase (TH) immunohistochemistry, and Fos protooncogene (C-Fos) immunofluorescence staining of the hypothalamus tissue. Results: Compared with RDN alone, RDN following intragastric DAPA administration reduced systolic blood pressure (SBP) in SHRs, independent of its hypoglycemic effect. Compared with the RDN group, the pathological results of the RDN+SGLT-2i group revealed a greater improvement in the intensity of TH staining in the hypothalamus tissue, closer to the normal level of the cross-sectional area in myocardial cells. Furthermore, we observed enhanced sympathetic inhibition in the brain and a reduction in the fibrotic area within myocardial cells. Additionally, the proportions of inflammatory mononuclear cell subsets and the levels of inflammatory factors improved. Although DAPA reduced inflammation and sympathetic nerve overexcitation alone, it could not completely reverse blood pressure (BP) or cardiac function. Similarly, the alleviation of inflammation and BP reduction in RDN-treated rats were inferior to those in rats treated with RDN combined with DAPA. Conclusions: Compared with RDN alone, DAPA addition before RDN can considerably reduce the BP of SHRs. The enhancement of the hypotensive effect may be attributed to the inhibition of sympathetic activity and the reduction in inflammatory reactions. |
| format | Article |
| id | doaj-art-30c296f06db94cebb0364ba957cd983d |
| institution | DOAJ |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-30c296f06db94cebb0364ba957cd983d2025-08-20T02:42:53ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-06-013063130910.31083/FBL31309S2768-6701(24)01625-3Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory ReactionHao Zhang0Zhuqing Li1Wei Cai2Yanxin Wang3Jiaxin Feng4Xuemei Yin5Qi Li6Ning Yang7Chengzhi Lu8Yuming Li9Department of Cardiovascular, Clinical School of Cardiovascular Disease, Tianjin Medical University, 300450 Tianjin, ChinaDepartment of Cardiovascular, Tianjin First Center Hospital, 300110 Tianjin, ChinaInstitute of Cardiovascular Disease, Characteristic Medical Center of People’s Armed Police Force, 300000 Tianjin, ChinaDepartment of Cardiovascular, The First Central Clinical School, Tianjin Medical University, 300110 Tianjin, ChinaDepartment of Cardiovascular, The First Central Clinical School, Tianjin Medical University, 300110 Tianjin, ChinaDepartment of Cardiovascular, The First Central Clinical School, Tianjin Medical University, 300110 Tianjin, ChinaSchool of Medicine, Nankai University, 300191 Tianjin, ChinaDepartment of Cardiovascular, Clinical School of Cardiovascular Disease, Tianjin Medical University, 300450 Tianjin, ChinaDepartment of Cardiovascular, Tianjin First Center Hospital, 300110 Tianjin, ChinaDepartment of Cardiovascular, Clinical School of Cardiovascular Disease, Tianjin Medical University, 300450 Tianjin, ChinaBackground: Sodium-dependent glucose transporter-2 inhibitors (SGLT-2i) have potential hypotensive effects, enhancing the hypotensive effect of renal denervation (RDN). Spontaneously hypertensive rats (SHRs) were used to verify this hypothesis and explore the associated underlying pathways. Methods: Seven Wistar-Kyoto (WKY) rats and 35 SHRs were divided into 6 groups. The blank WKY control (W) group consisted of all 7 WKY rats, whereas the SHRs were divided into the following groups, each containing 7 rats: sham operation (Sham), renal denervation (RDN), SGLT-2 inhibitor treatment (SGLT-2i), and the combination of renal denervation with SGLT-2 inhibitor treatment (RDN+SGLT-2i). The rats in the RDN+SGLT-2i and SGLT-2i groups were gavaged with dapagliflozin (DAPA) before RDN. The sham group was subjected to a sham operation. One-week post-operation, rat tail manometry, and echocardiography were subsequently performed, and peripheral blood inflammatory cells were detected via flow cytometry before sample collection. Following sample collection, the serum, including interleukin-6, angiotensin-II, renin, and norepinephrine, was tested via enzyme-linked immunosorbent assay. Pathological testing included Masson staining of the myocardial tissue, tyrosine hydroxylase (TH) immunohistochemistry, and Fos protooncogene (C-Fos) immunofluorescence staining of the hypothalamus tissue. Results: Compared with RDN alone, RDN following intragastric DAPA administration reduced systolic blood pressure (SBP) in SHRs, independent of its hypoglycemic effect. Compared with the RDN group, the pathological results of the RDN+SGLT-2i group revealed a greater improvement in the intensity of TH staining in the hypothalamus tissue, closer to the normal level of the cross-sectional area in myocardial cells. Furthermore, we observed enhanced sympathetic inhibition in the brain and a reduction in the fibrotic area within myocardial cells. Additionally, the proportions of inflammatory mononuclear cell subsets and the levels of inflammatory factors improved. Although DAPA reduced inflammation and sympathetic nerve overexcitation alone, it could not completely reverse blood pressure (BP) or cardiac function. Similarly, the alleviation of inflammation and BP reduction in RDN-treated rats were inferior to those in rats treated with RDN combined with DAPA. Conclusions: Compared with RDN alone, DAPA addition before RDN can considerably reduce the BP of SHRs. The enhancement of the hypotensive effect may be attributed to the inhibition of sympathetic activity and the reduction in inflammatory reactions.https://www.imrpress.com/journal/FBL/30/6/10.31083/FBL31309sodium-dependent glucose transporter-2 inhibitorblood pressurerenal denervationinflammationhypertension |
| spellingShingle | Hao Zhang Zhuqing Li Wei Cai Yanxin Wang Jiaxin Feng Xuemei Yin Qi Li Ning Yang Chengzhi Lu Yuming Li Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction Frontiers in Bioscience-Landmark sodium-dependent glucose transporter-2 inhibitor blood pressure renal denervation inflammation hypertension |
| title | Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction |
| title_full | Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction |
| title_fullStr | Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction |
| title_full_unstemmed | Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction |
| title_short | Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction |
| title_sort | sodium dependent glucose transporter 2 inhibitor enhances the hypotensive effect of renal denervation by inhibiting sympathetic activity and inflammatory reaction |
| topic | sodium-dependent glucose transporter-2 inhibitor blood pressure renal denervation inflammation hypertension |
| url | https://www.imrpress.com/journal/FBL/30/6/10.31083/FBL31309 |
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