Previous studies in the dog have demonstrated that intravascular mechanoreceptors have effects on renal excretory function via reflex modulation of arginine vasopressin, renin and catecholamine levels and efferent renal nerve activity. These afferent neural pathways are thus believed to provide the link between changes in blood volume and appropriate changes in salt and water excretion. It has been further hypothesized that a depressed sensitivity or resetting of these receptors may contribute to the fluid retention seen in heart failure and that the efficacy of cardiac glycoside treatment in this condition may be partially due to this treatment increasing the sensitivity of these receptor mechanisms. However, the role of these neural mechanisms in maintaining circulatory and body fluid homeostasis in the primate is still unclear. Studies using the primate model have demonstrated that afferent neural control of renal function in this species is less sensitive than in the dog and may be linked more to control of blood pressure than control of blood volume. Furthermore, it has been hypothesized that, unlike the dog, the renal nerves may not play a major role in directly affecting renal sodium reabsorption in the primate which suggests that efferent neural control of renal excretion may be less important in this species also. The studies in this proposal will extend these observations and more completely explore the possible importance of these neural mechanisms in the nonhuman primate.
The specific aims are: 1) to determine if acute and chronic renal denervation affect the antinatriuretic response to orthostasis and if chronic renal denervation causes the kidney to become hypersensitive to circulating norepinephrine, 2) to determine if there is interaction between atrial receptor and carotid sinus baroreceptor control of renal function and if cardiac glycoside treatment sensitizes these effects, (3) to determine if cardiac glycosides affect vagal cardiopulmonary baroreceptor and sinoaortic baroreceptor control of renal nerve activity during changes in blood volume. (4) To determine if vagal afferent pathways have tonic effects on arginine vasopressin, renin and catecholamine levels and baroreceptor interaction with these effects, (5) to directly determine the relative importance of cardiac receptors and baroreceptors in modulating the secretion of vasopressin, renin and catecholamines during changes in central blood volume and (6) to determine if cardiac receptors and/or baroreceptors are responsible for the interaction between volumetric and osmotic control of vasopressin.
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