Functioning of the hypothalamic-neurohypophyseal-vasopressin axis is altered in aging, and the pathway may represent a plausible target to slow the process of aging. Arginine vasopressin, a nine-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension, is central in this pathway. Vasopressin has important roles in circulatory and water homoeostasis mediated by vasopressin receptor subtypes V1a (vascular), V1b (pituitary), and V2 (vascular, renal). A dysfunction in this pathway as a result of aging can result in multiple abnormalities in several physiological systems. In addition, vasopressin plasma concentration is significantly higher in males than in females and vasopressin-mediated effects on renal and vascular targets are more pronounced in males than in females. These findings may be caused by sex differences in vasopressin secretion and action, making men more susceptible than females to diseases like hypertension, cardiovascular and chronic kidney diseases, and urolithiasis. Recently the availability of new, potent, orally active vasopressin receptor antagonists, the vaptans, has strongly increased the interest on vasopressin and its receptors as a new target for prevention of age-related diseases associated with its receptor-altered signaling. This review summarizes the recent literature in the field of vasopressin signaling in age-dependent abnormalities in kidney, cardiovascular function, and bone function.

Central hypovolemia induced by orthostatic loading causes reno-vascular changes that can lead to orthostatic intolerance. In this study, we investigated volume regulating hormonal responses and reno-vascular changes in male and female subjects as they underwent central hypovolemia, induced by graded lower body negative pressure (LBNP). Aquaporin-2 (AQP2) excretion was measured as a biomarker for the renal system response to vasopressin. 37 young healthy subjects (n = 19 males; n = 18 females) were subjected to graded LBNP until -40 mmHg LBNP. Under resting conditions, males had significantly higher copeptin (a stable peptide derived from vasopressin) levels compared with females. Adrenocorticotropin (ACTH), adrenomedullin (ADM), vasopressin (AVP) and brain natriuretic peptide (BNP) were not affected by our experimental protocol. Nevertheless, an analysis of ADM and BNP with the data normalized as percentages of the baseline value data showed an increase from baseline to 10 min after recovery in the males in ADM and in the females in BNP.Analysis of BNP and ADM raise the possibility of a preferential adaptive vascular response to central hypovolemia in males as shown by the normalized increase in ADM, whereas females showed a preferential renal response as shown by the normalized increase in BNP. Furthermore, our results suggest that there might be a difference between men and women in the Copeptin response to alterations in orthostatic loading, simulated either by using LBNP or during posture changes.

Adrenomedullin and galanin concentrations were similar between genders and did not change following adoption of the standing posture. To further clarify the roles, these hormones play in orthostatic intolerance, adrenomedullin and galanin concentrations should be assessed in participants who show presyncopal symptoms during an orthostatic challenge.

Galanin and adrenomedullin plasma responses to head-up tilt and lower body negative pressure have been studied previously. However, to what extent short-arm human centrifugation (SAHC) affects these responses is not known. In this study, we assessed how the application of variable gradients of accelerations (ΔGz) via shifting of the rotation axis during centrifugation affects selected hormonal responses. Specifically, we tested the hypothesis, that cardiovascular modulating hormones such as galanin and adrenomedullin will be higher in non-finishers (participants in whom at least one of the pre-defined criteria for presyncope was fulfilled) when compared to finishers (participants who completed the entire protocol in both sessions) during SAHC exposure. Twenty healthy subjects (10 women and 10 men) were exposed to two g-levels [1 Gz and 2.4 Gz at the feet (Gz_Feet)] in two positions (axis of rotation placed above the head and axis of rotation placed at the heart level). Elevated baseline levels of galanin appeared to predict orthostatic tolerance (p = 0.054) and seemed to support good orthostatic tolerance during 1 Gz_Feet SAHC (p = 0.034). In finishers, 2.4 Gz_Feet SAHC was associated with increased galanin levels after centrifugation (p = 0.007). For adrenomedullin, the hypothesized increases were observed after centrifugation at 1 Gz_Feet (p = 0.031), but not at 2.4 Gz_Feet, suggesting that other central mechanisms than local distribution of adrenomedullin predominate when coping with central hypovolemia induced by SAHC (p > 0.14). In conclusion, baseline galanin levels could potentially be used to predict development of presyncope in subjects. Furthermore, galanin levels increase during elevated levels of central hypovolemia and galanin responses appear to be important for coping with such challenges. Adrenomedullin release depends on degree of central hypovolemia induced fluid shifts and a subject’s ability to cope with such challenges. Our results suggest that the gradient of acceleration (ΔGz) is an innovative approach to quantify the grade of central hypovolemia and to assess neurohormonal responses in those that can tolerate (finishers) or not tolerate (non-finishers) artificial gravity (AG). As AG is being considered as a preventing tool for spaceflight induced deconditioning in future missions, understanding effects of AG on hormonal responses in subjects who develop presyncope is important.