Abstract P3131: Aquaglyceroporin Expression In Resistance-sized Arteries

Abstract

Due to its importance in maintaining homeostasis of many physiological processes in the body, including the cardiovascular system, it’s crucial that humans consume water, to replace any loss that occurs through urine, sweat, feces, and expelled air. Unfortunately, a significant proportion of the global population either does not have a safe drinking water source or consistent access to water throughout the year and with water scarcity projected to only impact more people in the future, it’s important to understand what is the effect of water deprivation on the human body. Once the body loses a greater amount of water than it’s able to intake it enters the process of dehydration, resulting in a body water deficit, known as hypohydration. Even mild dehydration can affect an individual's mental and physical well-being, with an association between chronic dehydration and adverse cardiovascular outcomes, including hypertension, stroke, and coronary heart disease (CHD). While the majority of research is focused on acute dehydration, chronic low water intake, also termed underhydration, is also associated with adverse health outcomes. However, the effect of acute and chronic reductions in water intake on the function of resistance-sized arteries, and particularly vascular smooth muscle cells (VSMCs), that regulate systemic blood pressure, is poorly understood. Aquaporins (AQPs) are membrane proteins primarily responsible for facilitating water movement across cells in tissues and organs, , with the aquaglyceroporin (AQP3, AQP7, AQP9-10), subfamily also exhibiting permeability to glycerol, and other small solutes. Previous studies have identified AQP7 expression in endothelial cells (ECs) and the heart, where it is proposed to enable the uptake of glycerol as a cardiac energy substrate, however, its function in VSMCs is unclear. Preliminary data demonstrate that in mice the expression of glycerol-permeable aquaglyceroporins, AQP7 and AQP9, are elevated in mesenteric arteries by 48 hours of water deprivation and 28 days of reduced water intake, respectively. Mesenteric artery glycerol content is higher in mice dehydrated for 48 hours compared to 0-hr controls. Male mice administered 10% glycerol ad libitum with water have elevated mesenteric artery AQP7 expression when compared to 0-hr controls. In female mice, ovariectomy (OVX) attenuates increased AQP7 expression in 48-hr dehydrated females, with, 17β-estradiol treatment restoring dehydrated-mediated elevations in expression. These findings suggest that mice adjust to alterations in water intake differently short- and long-term, and suggest a potential mechanism for increasing VSMC glycerol-uptake as an energy source during water duress.