SGLT2 抑制剂对雌性 Dahl SS 大鼠盐诱导性高血压的影响。
Effect of SGLT2 inhibition on salt-induced hypertension in female Dahl SS rats.
机构信息
Department of Molecular Pharmacology and Physiology, University of South Florida, 560 Channelside Dr., Tampa, FL, 33602, USA.
Hypertension and Kidney Research Center, University of South Florida, Tampa, FL, 33602, USA.
出版信息
Sci Rep. 2023 Nov 6;13(1):19231. doi: 10.1038/s41598-023-46016-z.
Sodium-glucose co-transporters (SGLTs) in the kidneys play a pivotal role in glucose reabsorption. Several clinical and population-based studies revealed the beneficial effects of SGLT2 inhibition on hypertension. Recent work from our lab provided significant new insight into the role of SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension, Dahl salt-sensitive (SS) rats. Dapagliflozin (Dapa) blunted the development of salt-induced hypertension by causing glucosuria and natriuresis without changes in the Renin-Angiotensin-Aldosterone System. However, our initial study used male SS rats only, and the effect of SGLT2 inhibitors on hypertension in females has not been studied. Therefore, the goal of this study was to determine whether SGLT2 inhibition alters blood pressure and kidney function in female Dahl SS rats. The result showed that administration of Dapa for 3 weeks prevented the progression of salt-induced hypertension in female rats, similar to its effects in male SS rats. Diuresis and glucose excretion were significantly increased in Dapa-treated rats. SGLT2 inhibition also significantly attenuated kidney but not heart fibrosis. Despite significant effects on blood pressure, Dapa treatment caused minor changes to electrolyte balance and no effects on kidney and heart weights were observed. Our data suggest that SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension blunts the development of salt-induced hypertension independent of sex.
肾脏中的钠-葡萄糖协同转运蛋白（SGLTs）在葡萄糖重吸收中发挥着关键作用。多项临床和基于人群的研究揭示了 SGLT2 抑制对高血压的有益作用。我们实验室的最新研究为 SGLT2 抑制在盐敏感型高血压非糖尿病模型（Dahl 盐敏感型（SS）大鼠）中的作用提供了重要的新见解。达格列净（Dapa）通过引起糖尿和利钠作用而不改变肾素-血管紧张素-醛固酮系统，从而减轻盐诱导的高血压的发展。然而，我们的初步研究仅使用了雄性 SS 大鼠，并且尚未研究 SGLT2 抑制剂对雌性高血压的影响。因此，本研究的目的是确定 SGLT2 抑制是否会改变雌性 Dahl SS 大鼠的血压和肾功能。结果表明，达格列净治疗 3 周可预防雌性大鼠盐诱导的高血压进展，其作用与雄性 SS 大鼠相似。在达格列净治疗的大鼠中，利尿和葡萄糖排泄明显增加。SGLT2 抑制还显著减轻了肾脏但不减轻心脏纤维化。尽管对血压有显著影响，但达格列净治疗仅引起电解质平衡的微小变化，对肾脏和心脏重量没有影响。我们的数据表明，SGLT2 抑制在盐敏感型高血压非糖尿病模型中可减轻盐诱导的高血压的发展，而与性别无关。
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