These studies have been designed to provide needed evidence regarding the nature of the mechanisms by which intrarenal agents, such as catecholamines and prostaglandins, participate in the regulation of renin release by the juxtaglomerular (JG) cells of the kidney of the active and hibernating ground squirrel. Although it has been generally assumed that hibernation is a steady-state phenomenon, recent studies concerning the functionality of the renin-angiotensin system during this state clearly contradict this notion. To prevent the influence of other in vivo factors which are known to also affect renin release in non-hibernating species, isolated renal cortical tissues preparations devoid of unwanted in vivo influences will be utilized in these studies. The experimental animals will be trapped in their habitat and maintained in individual cages with unlimited access to food and water. The experimental design involves the chronological evaluation of biochemical and ultrastructural alterations in the JG cells of this species during activity, hibernation, and the intermediate transitional states, both at rest and in response to stimulation by a variety of intrarenal agents. The experimental questions being asked are; whether or not the renin-secreting cells can respond to a stimulatory challenge during hibernation; whether catecholamines and prostaglandins can exert a direct action on renin release through mechanisms similar to those proposed for non- hibernating species; whether their effect is mediated by changes in intracellular cyclic nucleotide content; and whether their mode of action is reflected in changes in juxtaglomerular cell morphology as an index of synthesis, secretion, or both. Methods will include the in vitro incubation of isolated cells in the presence of various catecholamines and prostaglandins, of membrane receptor-agonist and antagonist agents, of protein synthesis inhibitors, and of exogenous cyclic nucleotides, followed by measurement of renin release and tissue cyclic GMP and AMP content by radioimmunoassay and evaluation of changes in juxtaglomerular cell morphology by electron microscopy. In addition to the fundamental questions these studies will attempt to answer, the study of the regulation of renin release using an animal model which undergoes drastically different seasonal physiological changes will be of significant scientific value, by providing chronological data of the adjustments in renin secretory activity which may be expected to occur as the animal modifies its blood pressure and electrolyte homeostasis when switching from the hibernating to the active state, and vice versa.
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