As opposed to the extensive information available for non-hibernating mammals, little is known about the nature of the mechanisms by which the sympathetic nervous system regulates blood pressure in hibernators via changes in renal renin secretion. Yet, because of their dramatic shifts in blood pressure during their circannual cycle, hibernators may constitute a unique animal model in which to evaluate the extent and mode of action of sympathetically-mediated influences on renin release during significantly different but chronologically coupled physiological states. Therefore, the long term goal of these in vitro studies is to chronologically elucidate some of the mechanisms by which sympathetic intrarenal catecholamines may directly, rather than indirectly, regulate renin release in the hibernator during the circannual cycle. To prevent the influence of other factors known to simultaneously affect renin release in the live animal, a renal cortical slice preparation from male and female golden-mantled ground squirrels will be utilized and renin release, tissue renin content, and tissue cyclic nucleotide content will be measured by radioimmunoassay. The specific objectives of these studies are: 1) to determine the extent of participation of alpha-,beta- and dopamine-receptor mechanisms in regulating renin release during activity and torpor; 2) to investigate if these receptor mechanisms utilize calcium and/or cyclic nucleotides as intracellular mediators and new renin synthesis as an obligatory step; 3) to evaluate whether seasonal changes in body temperature alter the responses of these receptor mechanisms to in vitro catecholamine challenge; 4) to elucidate what type of acute sympathetic mechanistic modification in renin release regulation occur during important transitional stages, such as periodic arousal from hibernating bouts; and 5) to determine if animal gender influences the renin release responses to catecholamine stimulation during the circannual cycle. In addition to the fundamental questions these studies will attempt to answer at the cellular level, 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 throughout its circannual cycle.
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