Vasopressin 2 receptors in the bat bladder: effects of age and biological sex on expression and function

ABSTRACT Nocturia, frequent night-time urination, has a major negative impact on sleep and health, particularly in the elderly. Changes in vasopressin release and the expression of vasopressin receptors are significant contributors to nocturia. A vasopressin analogue, desmopressin, is used clinically to treat nocturia. Desmopressin dosing must be titrated according to biological sex and age. However, its underlying mechanism of action is poorly understood because (1) vasopressin receptors are expressed in multiple tissues with multiple effects and (2) vasopressin release and vasopressin receptor expression vary with age and sex. In this pilot study, we propose to use the long-lived fruit bat, Carollia perspicillata, as a model system to establish the age- and sex- based changes in vasopressin signaling, with an emphasis on vasopressin 2 receptor (V2R) levels in the kidney and bladder. It has been established that the fruit bat is closer to humans in reproductive biology and neurobiology than rodents are to humans, suggesting that the bat may be a useful animal model. Critically, the fruit bat can live well over ten years in captivity, making it a potentially important model organism for studies of cumulative age-related changes in organ structure and function. In Aim 1, we will establish the prevalence of nocturia and polyuria in our bat colony and determine the distribution and expression levels of V2 receptors in the kidney and bladder wall and the impact of biological sex and age on these levels. In Aim 2, we will determine the impact of desmopressin treatment on urine output and osmolality and bladder capacity and contractility in young and elderly animals of both sexes. We will test the hypothesis that changes in urine output and osmolality and bladder function in animals of different age and sex depend on changes in vasopressin receptor expression levels. This pilot study will provide feasibility data on the fruit bat's utility as a model of natural aging in urobiology. Our results will support more detailed studies of the neuro-uro-biological mechanism of vasopressin for the study of targeted therapeutics in conditions such as nocturia.