The broad objective of the current application is to elucidate mechanisms which participate in the intrarenal regulation of sodium excretion. The specific objective of this proposal is to define intrarenal mechanisms of action of atrial natriuretic factor (ANF) in the control of sodium excretion. Based on previous work, we have formulated the working hypothesis that the """"""""physiologic"""""""" action of ANF is to increase sodium excretion in part by alterations in intrarenal hemodynamics which result in a synergistic action between an increase in renal interstitial hydrostatic pressure and an increase in medullary blood flow to decrease the reabsorption of sodium, effects which are modulated by intrarenal vasoconstrictor-vasodilator activity of the renin-angiotensin and renal prostaglandin systems respectively. To test this hypothesis, studies are proposed in the rat. Studies are also proposed in the aorto-caval rat and cardiomyopathic hamster to extend this hypothesis to an understanding of the role of ANF in congestive heart failure. The questions to be addressed are: 1. What is the """"""""physiologic"""""""" action of ANF on renal excretory and hemodynamic function? 2. Are ANF-mediated decreases in tubular reabsorption of sodium dependent upon an increase in renal interstitial hydrostatic pressure? 3. Does ANF increase medullary blood flow with subsequent medullary washout and is this increase dpendent upon an intact intrarenal prostaglandin system characteristic of other renal vasodilators? Is cGMP involved in a link between medullary hemodynamics and ANF natriuresis? 4. Does ANF-mediated inhibition of the intrarenal renin-angiotensin system (RAS) contribute to the natriuretic response to ANF and what is the mechanism for this contributing role? 5. Does elevated ANF, which is characteristic of heart failure, maintain renal function and attenuate the increase in the renin-angiotensin system (RAS) despite a reduction in renal perfusion pressure? 6. Is the renal """"""""hyporesponsiveness"""""""" to ANF in a model of heart failure mediated by enhanced activity of the RAS and/or alterations in renal interstitial hydrostatic pressure (Pi)?
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