Laboratory of Experimental Hypertension, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Physiol Res. 2024 Apr 18;73(Suppl 1):S377-S387. doi: 10.33549/physiolres.935364.
A new class of antidiabetic drugs - gliflozins (inhibitors of sodium glucose cotransporter-2; SGLT-2i) stimulate glucose and sodium excretion, thereby contributing to improved glycemic control, weight loss and blood pressure reduction in diabetic patients. Large clinical trials in patients with type 2 diabetes treated with empagliflozin, canagliflozin or dapagliflozin have demonstrated their excellent efficacy in improving many cardiovascular outcomes, including the reduction of death from cardiovascular diseases, non-fatal myocardial infarction or stroke, and hospitalization for heart failure. Moreover, the beneficial effects of SGLT-2i were also demonstrated in the decrease in proteinuria, which leads to a lower risk of progression to end-stage renal disease and thus a delay in initiation of the renal replacement therapy. Unexpectedly, their cardioprotective and renoprotective effects have been demonstrated not only in patients with diabetes but also in those without diabetes. Recently, much effort has been focused on patients with heart failure (either with reduced or preserved ejection fraction) or liver disease. Experimental studies have highlighted pleiotropic effects of SGLT-2 inhibitors beyond their natriuretic and glycosuric effects, including reduction of fibrosis, inflammation, reactive oxygen species, and others. Our results in experimental non-diabetic models of hypertension, chronic kidney disease and heart failure are partially consistent with these findings. This raises the question of whether the same mechanisms are at work in diabetic and non-diabetic conditions, and which mechanisms are responsible for the beneficial effects of gliflozins under non-diabetic conditions. Are these effects cardio-renal, metabolic, or others? This review will focus on the effects of gliflozins under different pathophysiological conditions, namely in hypertension, chronic kidney disease, and heart failure, which have been evaluated in non-diabetic rat models of these diseases. Key words: SGLT-2 inhibitor, hypertension, chronic kidney disease, heart failure, liver disease, rat.
一类新型的抗糖尿病药物——葡萄糖协同转运蛋白 2（SGLT-2）抑制剂，可促进葡萄糖和钠的排泄，从而改善糖尿病患者的血糖控制、体重减轻和血压降低。在接受恩格列净、卡格列净或达格列净治疗的 2 型糖尿病患者的大型临床试验中，已证实其在改善多种心血管结局方面的卓越疗效，包括降低心血管疾病死亡、非致死性心肌梗死或卒中以及心力衰竭住院的风险。此外，SGLT-2 抑制剂还可减少蛋白尿，从而降低进展为终末期肾病的风险，进而延迟开始肾脏替代治疗，从而降低蛋白尿。出乎意料的是，其心脏保护和肾脏保护作用不仅在糖尿病患者中，而且在非糖尿病患者中也得到了证实。最近，人们对心力衰竭（射血分数降低或保留）或肝病患者的关注度有所提高。实验研究强调了 SGLT-2 抑制剂除了利尿和降糖作用之外的多种作用机制，包括减少纤维化、炎症、活性氧等。我们在实验性非糖尿病高血压、慢性肾脏病和心力衰竭模型中的结果与这些发现部分一致。这就提出了一个问题，即在糖尿病和非糖尿病情况下，是否存在相同的作用机制，以及在非糖尿病情况下，SGLT-2 抑制剂的有益作用是由哪些机制引起的。这些作用是心脏-肾脏、代谢还是其他方面的？本综述将重点关注 SGLT-2 抑制剂在不同病理生理条件下的作用，即在高血压、慢性肾脏病和心力衰竭的非糖尿病大鼠模型中进行评估。关键词：SGLT-2 抑制剂、高血压、慢性肾脏病、心力衰竭、肝病、大鼠。
