Age-Dependent Changes in the Relationships between Traits Associated with the Pathogenesis of Stress-Sensitive Hypertension in ISIAH Rats

Abstract

Hypertension is one of the most significant risk factors for many cardiovascular diseases. At different stages of hypertension development, various pathophysiological processes can play a key role in the manifestation of the hypertensive phenotype and of comorbid conditions. Accordingly, it is thought that when diagnosing and choosing a strategy for treating hypertension, it is necessary to take into account age, the stage of disorder development, comorbidities, and effects of emotional-psychosocial factors. Nonetheless, such an approach to choosing a treatment strategy is hampered by incomplete knowledge about details of age-related associations between the numerous features that may contribute to the manifestation of the hypertensive phenotype. Here, we used two groups of male F₂(ISIAHxWAG) hybrids of different ages, obtained by crossing hypertensive ISIAH rats (simulating stress-sensitive arterial hypertension) and normotensive WAG rats. By principal component analysis, the relationships among 21 morphological, physiological, and behavioral traits were examined. It was shown that the development of stress-sensitive hypertension in ISIAH rats is accompanied not only by an age-dependent (FDR < 5%) persistent increase in basal blood pressure but also by a decrease in the response to stress and by an increase in anxiety. The plasma corticosterone concentration at rest and its increase during short-term restraint stress in a group of young rats did not have a straightforward relationship with the other analyzed traits. Nonetheless, in older animals, such associations were found. Thus, the study revealed age-dependent relationships between the key features that determine hypertension manifestation in ISIAH rats. Our results may be useful for designing therapeutic strategies against stress-sensitive hypertension, taking into account the patients' age.

Keywords: ISIAH rat strain; age-related difference; hypertension; principle component analysis; stress reactivity.

Figure 1

Principal component analysis performed on the combined group of male F₂(ISIAHxWAG) hybrids of different ages. Blue dots: 3–4-month-old rats; red dots: 6–7-month-old rats.

Figure 2

Principal component analysis in groups of F₂(ISIAHxWAG) hybrid males of different ages: (a) 3–4 months old; (b) 6–7 months old.

Figure 3

Principal component analysis (of behavioral traits) performed on the combined group of F₂(ISIAHxWAG) hybrid males of the two age ranges. Blue dots: 3–4-month-old rats; red dots: 6–7-month-old rats.

Figure 4

Principal component analysis of behavioral traits in groups of F₂(ISIAHxWAG) hybrid males of different ages: (a) 3–4 months old; (b) 6–7 months old.

Figure 5

An outline of experimental data collection. BP: blood pressure; Cort.: corticosterone. Days 1–4: open field test; day 8: basal BP measurement; day 15: BP measurement under stress and blood collection for corticosterone quantification under stress; day 22: decapitation, blood collection for basal corticosterone quantification, and body and organ weight measurement.