The prevalence of hypertension increases with age and is the leading modifiable risk factor for cognitive impairment and dementia. At present, the neural mechanisms promoting hypertension across the lifespan are incompletely understood. Using the Sprague–Dawley (SD) rat as a model of normal aging, we hypothesized (1) blood brain barrier (BBB) disruption and neuroinflammation in the paraventricular nucleus (PVN) of the hypothalamus enhances sympathetic tone and contributes to age-dependent hypertension, (2) age-dependent hypertension is associated with cognitive impairment, and (3) lowering blood pressure in aged rats with established hypertension improves cognitive function. We found male, but not female, rats develop age-dependent hypertension with enhanced sympathetic tone, BBB disruption, and neuroinflammation in the PVN. Aged hypertensive male rats also showed impairments in recognition and spatial memory. Utilizing pharmacological interventions, blood pressure was lowered in male rats with established hypertension using either losartan (LOS) or hydrochlorothiazide. However, only losartan improved recognition memory. Further, LOS reduced BBB disruption, microglial activation, astrocyte reactivity, and proinflammatory cytokine expression in the PVN which we speculate contributes to a decrease in blood pressure. These data show SD rats develop age-dependent hypertension and cognitive impairment in a sex-dependent manner. However, not all antihypertensive agents improve cognitive function equally as only losartan, an angiotensin II type 1 receptor antagonist (AT1R) improved recognition memory. Thus, AT1R antagonists represent a potential therapeutic approach for treating cognitive decline in the aging population.

高血压的患病率随着年龄的增长而增加，是认知障碍和痴呆的主要可改变危险因素。目前，在一生中促进高血压的神经机制尚不完全清楚。使用 Sprague-Dawley （SD） 大鼠作为正常衰老的模型，我们假设 （1） 下丘脑室旁核 （PVN） 的血脑屏障 （BBB） 破坏和神经炎症增强了交感神经张力并导致年龄依赖性高血压，（2） 年龄依赖性高血压与认知障碍相关，以及 （3） 降低患有高血压的老年大鼠的血压可改善认知功能。我们发现雄性（而不是雌性）大鼠发展为年龄依赖性高血压，伴有 PVN 中的交感神经张力增强、BBB 破坏和神经炎症。老年高血压雄性大鼠也表现出识别和空间记忆障碍。利用药物干预，使用氯沙坦 （LOS） 或氢氯噻嗪降低已确诊高血压的雄性大鼠的血压。然而，只有氯沙坦提高了识别记忆。此外，LOS 减少了 PVN 中的 BBB 破坏、小胶质细胞活化、星形胶质细胞反应性和促炎细胞因子表达，我们推测这有助于降低血压。这些数据表明 SD 大鼠以性别依赖性方式发展为年龄依赖性高血压和认知障碍。然而，并非所有降压药都能像只有血管紧张素 II 1 型受体拮抗剂 （AT1R） 氯沙坦那样改善认知功能。因此，AT1R 拮抗剂代表了治疗老龄化人群认知能力下降的潜在治疗方法。