Diabetes mellitus type 2 (T2DM) is characterized by resistance of insulin receptors and/or inadequate insulin secretion resulting in metabolic and structural complications including vascular diseases, arterial hypertension and different behavioral alterations. We aimed to study the effects of the antihypertensive angiotensin AT1 receptor antagonist losartan on the T2DM-induced changes of exploratory behavior, anxiety, nociception and short term memory in normotensive Wistar and spontaneously hypertensive rats (SHRs). The experimental model of T2DM induced by a combination of high fat diet and streptozotocin, decreased exploratory activity and increased the level of carbonylated proteins in selected brain structures in both strains; as well it increased corticosterone level, pain threshold, anxiety-like behavior, and decline short term memory only in SHRs. Losartan treatment alleviated some of the T2DM- induced metabolic complications, abolished the T2DM-induced hypo activity, and normalized the corticosterone level, carbonylated proteins in brain, nociception and memory. Losartan did not exert effect on the anxiety behavior in both strains. We showed that T2DM exerted more pronounced negative effects on the rats with comorbid hypertension as compared to normotensive rats. Overall effects on the studied behavioral parameters are related to decreased exploration of the new environment, increased anxiety-like behavior, and decline in short-term memory. The systemic sub-chronic treatment with an angiotensin AT1 receptor antagonist losartan ameliorated most of these complications.

中文翻译：

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氯沙坦对 Wistar 和自发性高血压大鼠中某些 2 型糖尿病引起的并发症的保护作用。

2 型糖尿病 (T2DM) 的特点是胰岛素受体抵抗和/或胰岛素分泌不足，导致代谢和结构并发症，包括血管疾病、动脉高血压和不同的行为改变。我们的目的是研究抗高血压血管紧张素 AT1 受体拮抗剂氯沙坦对正常血压 Wistar 和自发性高血压大鼠 (SHR) 的 T2DM 探索行为、焦虑、伤害感受和短期记忆变化的影响。由高脂肪饮食和链脲佐菌素联合诱导的 T2DM 实验模型，在两种菌株的选定大脑结构中降低了探索活动并增加了羰基化蛋白质的水平；它还会增加皮质酮水平、痛阈、焦虑样行为，并仅在 SHR 中降低短期记忆。氯沙坦治疗缓解了一些 T2DM 引起的代谢并发症，消除了 T2DM 引起的活动不足，并使皮质酮水平、大脑中的羰基化蛋白、伤害感受和记忆正常化。氯沙坦对两种菌株的焦虑行为均没有产生影响。我们发现，与血压正常的大鼠相比，T2DM 对合并高血压的大鼠产生更明显的负面影响。对所研究的行为参数的总体影响与对新环境的探索减少、焦虑样行为增加和短期记忆下降有关。使用血管紧张素 AT1 受体拮抗剂氯沙坦进行全身亚慢性治疗可改善大部分并发症。