This research proposal is intended to provide new information on the mechanisms involved in the functional and biochemical changes which occur after reduction in functioning renal mass produced by acute unilateral nephrectomy (AUN) or unilateral ureteral occlusion (uuo). These maneuvers influence the rate of cation (sodium and potassium) excretion by the contralateral kidney. In the case of AUN, a hemodynamic signal involving carotid sinus baroreceptors initiates the reflex increase in cation excretion, while in the case of uuo, renal afferent nerves may be responsible for initiating increased cation excretion by the contralateral kidney. Recent studies indicate that the opiate antagonist naloxone prevents the increased cation excretion after these maneuvers. The proposed research evaluates the role of the endogenous opioid system in these reflex adjustments by carrying out AU:N and UUO in animals made tolerant to the effects of morphine sulfate. Additional studies will determine if the opiate receptor involved in the responses to these maneuvers resides in the central nervous system or in the periphery. The relationship of the acute functional changes occurring after AUN or UUO to the initiation of compensatory renal growth will be tested by examining the effect of these reductions in functioning renal tissue on activity of the enzyme ornithine decarbosylase (EC 4.1.1.17) in the contralateral kidney in normal animals and animals infused acutely with naloxone. The long-term consequences of AUN and UUO on compensatory hypertrophy will be determined in animals with continuous opiate receptor blockade or tolerance and in animals in which ODC activity has been inhibited. These studies will provide important new information on the regulation of blood volume and sodium excretion which will have direct relevance to states of altered physiology such as hypertension and the pathological retention of sodium by the kidneys. The studies will also gain insight into the mechanism leading to compensatory renal growth. In particular, they will provide new understanding on the role of circulating factors which may lead to the functional adaptation as well as the compensatory hypertrophy after reductions in functioning renal tissue.
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