Effect of social isolation stress on sex differences in age-related changes of vascular sensitivity to arginine vasopressin and expression of vasopressin and glucocorticoid receptors in the rat aorta and myocardium
Abstract
In the modern society, social and demographic changes have increased the prevalence of loneliness and social isolation, especially among senior people. Old age and chronic psychosocial stress are independent risk factors for cardiovascular disease. The aim was to study the effect of social isolation stress on sex differences in age-related changes of vascular sensitivity to arginine-vasopressin (AVP) and the expression of vasopressin and glucocorticoid receptors in the rat aorta and myocardium.
Methods. Social isolation stress was modeled by isolating rats in individual cages from the age of 22 months through 24 months. The contraction force of isolated blood vessels was measured in the isometric mode with a four-channel myograph (Danish Myo Technology, Multi Myograph System – 620M). Gene expression was assessed by the PCR analysis.
Results. In old (24 months) rats, the strength of the contractile response to AVP was significantly increased. As distinct from males, in females, not only the contraction force but also the duration of AVP-induced tonic reaction was increased. In both young and old females, the aorta sensitivity to AVP was 2.7 and 2.2 times higher than in males, respectively. Blood vessels showed sex differences in the age-related changes of the vasopressin receptor V1 (V1AR) expression profile: in old females, the mRNA level was decreased 1.4 times, while in old males, in contrast, mRNA was twofold increased compared to young rats. In old rats, regardless of the gender, the glucocorticoid receptor (GR) gene expression was significantly increased in right and left atria, the area of the most important regulators of the electrical pulse passage between the atria and the ventricles. Social isolation stress had no significant effect on the age-related changes in vascular reactivity to AVP and the V1AR and GR gene expression. Prolonged, chronic stress induced a significant increase in the cardiac V1AR expression in old male rats and, on the contrary, a decrease in old females. Isolation stress in old females induced a decrease, while in old males, it induced an increase in the left ventricular GR gene expression.
Conclusion. One of the mechanisms for the increased agonist-induced vasoconstrictor response in old male rats is a high level of AV1AR gene expression. The stronger and more lengthy vasoconstrictor reaction of old female rats associated with the decreased AV1AR gene expression suggests that the Rho-kinase cascade plays a significant role in their regulation of vascular tone, since the cascade activation can influence not only the contraction force but also its kinetics. The age-related increase in the atrial GR gene expression in old male and female rats may be a mechanism underlying disorders of both the heart rhythm and hemodynamics. The adverse impact of social isolation stress is more pronounced in the heart of old rats.
