ArticleGeroScience2025
Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague-dawley rat.
Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Risk of Dementia With Renin-Angiotensin System Inhibitors Versus Calcium Channel Blockers in Hypertensive Adults: A Nationwide Multicenter Study.Drugs & aging · 2026Article
- Recent developments and challenges in hypertensive dementia over the past year.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Article
- Cortical OProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Brain AT1 and AT2 receptors and nitric oxide in baroreflex regulation of renal sympathetic activity in unanaesthetised rats.Scientific reports · 2025Article
- Age-Related Alterations of Cerebral Autoregulation.Life (Basel, Switzerland) · 2025Review
- Potential role of nanopharmacology in reducing neuroinflammation associated with hypertension and metabolic disorders.World journal of experimental medicine · 2025Review
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
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Authors and funding
7 authors.
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Abstract
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.
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