Vasopressin receptor regulation response to cold stress in a pig model of hypothermia

In response to acute cold stress, vasoconstriction of specific vascular beds over others helps stem core body temperature loss, slow metabolism and sustain renal function. We hypothesized that differential distribution of vasopressin (VP) receptors in various vascular beds may help modulate redirection of blood flow in response to hypothermia per se without stimulation of VP synthesis response to hypotension or hypoxemia. The objective of this project was to characterize VP receptor up- or downregulation and changes in VP mRNA expression in cold stress. Anesthetized, mechanically ventilated Duroc cross young pigs were catheterized and then either kept normothermic at 38.4 + 0.1 oC (warm, n=14) or sustained hypothermia (34.5 + 0.1 oC) for 2 to 4 hours (cold, n=20). Hemodynamics, blood gasses, and core body temperature were monitored throughout with regional blood flow assessed via colored microspheres. Plasma samples were obtained for endocrine analysis of VP, aldosterone, cortisol, renin activity, adrenocorticotropic hormone, and norepinephrine. At the end of the experiment, tissues and arteries of different vascular beds were harvested for assessment of VP mRNA or VP receptor V1aR or V2R mRNA. Hypothermia was achieved with no change in mean arterial pressure (66 + 3 mmHg in both warm and cold groups) despite a cold-induced slowing of metabolism indicated by a decrease in heart rate. Circulating neuroendocrine hormone levels were not significantly different between warm and cold pigs. Hypothalamus VP mRNA expression and VP synthesis was not changed with acute cold exposure in accord with no change in VP plasma levels (11.1+1.4 uU/ml in warm vs 10.9 + 1.1 uU/ml in cold). V1aR mRNA expression was highest in the carotid artery, celiac trunk, and renal arteries compared to mesenteric artery, aorta and pulmonary arteries. V2R mRNA expression was highest in renal arteries and celiac trunk compared to carotid >mesenteric >aorta > pulmonary arteries. VP receptor V1aR and V2R expression was consistent with observed cold-induced blood flow changes. Carotid V1aR expression and aorta V2R expression were decreased (p< 0.05) with cold exposure. Depletion of V1aR in carotid arteries was congruent with vasoconstriction leading to reduced brain blood flow. V2R endothelial mediated vasodilation in the thoracic aorta corresponded with cold-induced increased flow to the upper splanchnic bed. VP receptor expression also indicated regional modulation of blood flow within distinct areas of the kidney with cold causing a decrease in V2R expression in the renal cortex not seen in the medulla or papilla and a decrease V1aR expression in the medulla not seen in the cortex or papilla. Renal cortex V2R expression in cold exposure may reflect V2R mediation of glomerular arteriole vasodilation invoked to maintain glomerular filtration. Renal medulla V1aR expression changes may influence fluid and electrolyte uptake in the renal medullary capillary network. VP receptor expression reflects a role in regulating regional blood flow distribution in hypothermia, including targeted hemodynamic changes within the kidney that may be important in maintaining renal fluid and electrolyte homeostasis in the thermoregulatory response to hypothermia. The views expressed are those of the authors and do not necessarily reflect the official policy or position of the Defense Health Agency, Department of the Army, or the U.S. Government. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.