Integrative mechanisms of sex- and age-dependent hypertension and its impact on cognition
Embargo Date
2028-02-05
OA Version
Citation
Abstract
Hypertension is the leading modifiable risk factor for stroke, myocardial infarction, and chronic kidney disease. The prevalence of hypertension increases with age and impacts 1.4 billion individuals globally. Further, postmenopausal women are at a higher risk of developing hypertension. Although it is known that the salt sensitivity of blood pressure increases risk, hypertension is a complex disease that is influenced by multiple organ systems including the nervous and renal systems. Hypertension is also a modifiable risk factor for cognitive impairment, a major concern in the aging population. Due to the complexities of the pathophysiology of hypertension, underlying mechanisms such as factors affecting age-related hypertension are still being elucidated. Blood pressure is modulated in part by fluid and electrolyte balance which is influenced by the renal nerves and sympathetically mediated sodium chloride cotransporter activity. The renal nerves form a tightly regulated reflex to modulate fluid and electrolyte balance that is integrated in the paraventricular nucleus of the hypothalamus (PVN)- a critical autonomic integration center. Neuroinflammation and blood brain barrier disruption in the PVN can promote excess sympathetic outflow promoting hypertension. The hippocampus is a region of the brain critical for learning and memory and neuroinflammation in this region is associated with cognitive impairment. Attenuation of neuroinflammation in both the PVN and hippocampus lowers blood pressure and reduces sympathetic outflow, and improves cognition, respectively. Overall, hypertension research on the aging population is lacking, and thus advances in our understanding of the integrative renal and neural mechanisms that influence blood pressure as well as blood pressure’s impact on cognitive function may yield valuable information for treating high blood pressure and its consequences in the aging population. In this body of work, we used Sprague-Dawley, Dahl Salt Resistant, and Dahl Salt Sensitive rats to address fundamental gaps in our knowledge through the following aims: 1.) to examine the impact of sex, strain, and aging on hypertension, the salt sensitivity of blood pressure, and renal sodium reabsorption 2.) to assess the impact of aging and sex on blood brain barrier disruption and neuroinflammation in age-dependent hypertension and its association with cognitive impairment, and 3.) to assess the impact of an angiotensin II type 1 receptor antagonist to treat and prevent cognitive impairment in established hypertension and midlife hypertension. Understanding the integrative mechanisms driving hypertension and the salt sensitivity of blood pressure as well as the contributions of age-dependent hypertension to cognitive impairment has the potential to improve the treatment and prevention of hypertension and its comorbidities in the aging population and improve healthy aging.
Description
2025