In healthy people, the renin–angiotensin–aldosterone system (RAAS) is important to maintain homeostasis in blood pressure control. Depression increases the incidence of hypertension 10, and clinical symptoms of depression were reported to be associated with elevated blood pressure in elderly adults and women 11, 12.
Depression can be a risk factor for cardiovascular disease development, which in turn is associated with hypertension 7, 8, 9. Men with cardiovascular disease, including hypertension, were prone to depressive symptoms, and consequently, depression and general anxiety disorder 5, 6. Although the direct correlation is controversial 2, 3, 4, hypertension seemed to be closely related to depression. People with a chronic somatic disease like cancer, heart disease, and hypertension are relatively more at risk of psychological distress than are healthy people 1.
Researchers have tried to establish a relationship between medical illness and mental disorders. These might suggest possible mechanism on depressive symptom in chronic hypertensive state. Our results indicate that ANGII can induce depressive-like behaviors via microglial activation in the hippocampus and HPA axis hyperactivation in mice. In addition, ANGII treatment also induced the pro-inflammatory changes in BV-2 microglial cells. The molecular and behavioral changes by chronic ANGII infusion were reversed by co-treatment of minocycline or telmisartan. However, subacute ANGII infusion did not induce significant molecular and behavioral changes in mice compared to that of control. In addition, chronic ANGII infusion activated the hypothalamic–pituitary–adrenal axis (HPA axis) and resulted in decreased hippocampal glucocorticoid receptor level. Chronic infusion of ANGII also induced microglial activation in the hippocampus with increase of Il-1β mRNA and decrease of Arg1 mRNA. Chronic infusion of ANGII into mice induced depressive-like behaviors, including the tail suspension test and forced swimming test, which were reversed by imipramine. To address this issue, ANGII-containing osmotic pumps were implanted into adult male C57BL/6 mice subcutaneously for subacute (7 days) and chronic (at least 21 days) periods and behavioral and molecular analyses were conducted.
However, there is no animal study showing the direct relationship between ANGII and depression. Angiotensin II (ANGII), which is associated with hypertension, also induces brain inflammation. Brain inflammation is one of hypotheses explaining complex pathomechanisms of depression.
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