The Effect of Acute and Chronic Hydration Changes on Vascular Aquaporin Expression

Abstract

Introduction: The human body's homeostatic balance, particularly within cardiovascular function, relies heavily on adequate water intake to replenish losses from urine, sweat, feces, and respiration. The pressing issue is that a significant segment of the global populace lacks access to safe drinking water or faces inconsistent availability, a situation that is expected to worsen, heightening the urgency to understand water deprivation's physiological impacts. Dehydration, or hypohydration, manifests when water loss exceeds intake, with even minor instances compromising mental and physical health and correlating with detrimental cardiovascular consequences like hypertension, stroke, and coronary heart disease. While most research is focused on acute dehydration, chronic insuffcient water consumption, also known as underhydration, is also associated with similar negative effects on health. Despite this, the influence of acute and chronic water intake reduction on resistance-sized arteries and vascular smooth muscle cells (VSMCs), crucial in blood pressure regulation, remains inadequately explored. Aquaporins (AQPs) are membrane proteins facilitating cellular water transport, while the aquaglyceroporins (AQP3, AQP7, AQP9-10) subfamily also allows glycerol and other small solutes to permeate, are implicated in this process. While AQP7 function has been studied previously in the cardiovascular system, particularly its role in cardiac glycerol uptake, little is known regarding its function in systemic arteries that regulate blood pressure. Study Objective: The objective of this study is to understand the effects of dehydration and chronic reduced water intake on the expression of aquaglyceroporins, as well as resistance-sized arterial function, particularly in VSMCs, which are crucial for regulating systemic blood pressure. Hypothesis: The hypothesis is that dehydration will result in an elevation of the expression of glycerol-permeable aquaporins (AQP7 and AQP9) in resistance-sized artery VSMCs, elevating cellular glycerol content. Methodology: The study involves either inducing dehydration in C57BL/6J and AQP9−/− mice through water deprivation for 48 hours or restricting water intake for 28 days to investigate the expression of aquaporins (AQPs) in mesenteric arteries. In addition, the effects of glycerol supplementation (7 days ad libitum) and estrogen were also determined on AQP7 expression in male and ovariectomized female mice, respectively. Changes in message and protein expression were determined by RT-qPCR and Simple Western, respectively. Data: The data includes plasma osmolarity and glycerol concentration after 48 hours of dehydration, in C57BL/6J and AQP9−/− mice. Aquaglyceroporin expression levels were determined in mesenteric arteries following periods of dehydration, reduced water intake, and glycerol supplementation, in C57BL/6J and AQP9−/− mice. Summary of Results: Preliminary results indicate that water deprivation for 48 hours increases the expression of AQP7 in mouse mesenteric arteries, compared to controls, whereas 28 days of reduced water intake results in an elevation in AQP9 expression. Glycerol supplementation for 7 days, also results in elevated AQP7 expression levels, whereas, in contrast, AQP7 expression is not elevated in mesenteric arteries isolated from ovariectomized females. mice, with a concurrent increase in mesenteric artery glycerol content. AQP9−/− mice have higher plasma glycerol levels compared to controls, however, dehydration-mediated elevation in AQP7 expression is not attenuated by AQP9 KO. Conclusions: The study concludes that mice exhibit differential responses to short-term and long-term alterations in water intake, with changes in the expression of aquaglyceroporins in resistance-sized arteries, potentially increasing glycerol uptake into VSMCs providing an energy source during periods of water scarcity. This work was supported by American Heart Association AIREA grant number 947620. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.