Chronic exposure of laboratory rats to cold is accompanied by an increase in heat production (metabolic rate), an increase in circulating catecholamine levels, and an increase in the metabolic responsiveness to peripheral administration of norepinephrine. The latter characterizes the cold-adapted rat. In contrast, the vascular reactivity to administration of norepinephrine is reduced in the cold-adapted rat, yet resting blood pressure is significantly elevated. The objectives of these studies are to understand the state of receptors for catecholamines and angiotensin II (AII) in the brain and peripheral tissues of rats exposed to cold for varying period of time in order to assess their contribution to the elevation of blood pressure during exposure to cold. These changes will be correlated with the changes in plasma (corticosterone, aldosterone, catecholamines, plasma renin activity) and brain (catecholamine) hormone levels occurring during exposure to cold, as well as to the metabolic and cardiovascular (blood pressure and heart rate) responsiveness of cold-adapted rats to exogenously administered catecholamines and AII. These studies will be carried out at intervals after exposure to cold (5 degrees C.) for 4 weeks. Expts 3 and 4 are designed to determine the mechanisms underlying hormonal and receptor changes seen during exposure to cold. Expt 3 will be carried out in warm-adapted rats to assess the relationship among hormones, neurotransmitters and their respective receptors in central and peripheral tissues. The effect of chronic infusions (via osmotic minipumps) of aldosterone, corticosterone, norepinephrine, and AII, alone and combined, on plasma levels of corticosterone, aldosterone, catecholamines, and plasma renin activity, as well as on central AII, alpha 1 - and alpha 2 - adrenoceptors and catecholamine concentration will be studied. In addition, peripheral beta-receptor state in heart and brown adipose tissue, as well as alpha-adrenoceptors in mesenteric artery, and AII receptors in mesenteric artery and adrenal cortex will be assessed. Further studies (Expt 4) will utilize primary neuronal cultures of one day old rats to study, under relatively defined conditions, the effect of neurohormones, as well as steroid hormones, on the density and affinity of alpha- and beta- adrenoceptors and AII receptors for their ligands. In addition, the effects of hormones on the levels and turnover of catecholamines and immunoreactive AII in neuronal cultures will be examined.
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