The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases

Abstract

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

Keywords: ACTH; AVP; CRH; androgens; cardiac failure; estrogens; glucocorticoids; hypertension; mineralocorticoids; stress.

Figure 1

Flow diagram showing the sites of the synthesis, action, and interaction of vasopressin and hormones of the hypothalamo–pituitary–adrenal axis in the central nervous system and peripheral organs. Green arrows—stimulatory effects; red arrows—inhibitory effects. Blue arrows—complex effects (stimulatory or inhibitory, see text for explanations). Abbreviations: AChR—aceytolcholine receptor; ACTH—adrenocorticotropic hormone; AR—androgen receptor; CAT—catecholamine; CATR—catecholamine receptor; CRHR—corticotropin releasing hormone receptor; ESR—estrogen receptor; FSH—follicle-stimulating hormone; GC—glucocorticoid; GnRH—gonadotropin-releasing hormone; GR—glucocorticoid receptor; LH—luteinizing hormone; MC—mineralocorticoid; MR—mineralocorticoid receptor; V1aR—vasopressin V1a receptor; V1bR—vasopressin V1b receptor; V2R—vasopressin V2 receptor.

Figure 2

The regulation of the secretion of hormones of the hypothalamo–pituitary–adrenal axis. ACTH—adrenocorticotropic hormone, AVP—arginine vasopressin, CRH—corticotropine-releasing hormone, FSH—follicle-stimulating hormone; GnRH—gonadotropine-releasing hormone, LH—luteinizing hormone, + stimulation, - inhibition. Other explanations are in the text.

Figure 3

Steps of the synthesis of steroid hormones in the adrenal glands and gonads. Other explanations are in the text.

Figure 4

The phenomenon of “corticosteroid escape”. (A)—under normal conditions, corticosteroids inhibit the release of corticotrpine-releasing hormone (CRH), (B)—during inflammatory states, the activation of autoimmune processes’ and inhibition of CRH secretion via negative feedback are impaired and the activation of the HPA is maintained in spite of the high concentration of corticosteroids. ACTH—adrenocorticotropic hormone, IL-6—interleukin 6, green arrows—stimulation, purple (red) arrows—inhibition.

Figure 5

The stimulatory and inhibitory interactions between vasopressin and hormones secreted by the hypothalamo–pituitary–adrenal system that play essential roles in the regulation of energy balance, water–electrolyte balance, and blood pressure. ANS—autonomic nervous system, AVP—arginine vasopressin, GR—glucocorticoid receptor, MR—mineralocorticoids receptor, V1R, V1aR, and V1bR—vasopressin receptors. See text for further explanations.