INTRARENAL REGULATION OF SODIUM EXCRETION

Project: Research project

Description

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)?
StatusActive
Effective start/end date4/1/873/31/20

Funding

  • National Institutes of Health
  • National Institutes of Health: $270,375.00
  • National Institutes of Health
  • National Institutes of Health: $208,787.00
  • National Institutes of Health: $279,024.00
  • National Institutes of Health: $397,500.00
  • National Institutes of Health: $371,573.00
  • National Institutes of Health: $321,750.00
  • National Institutes of Health: $394,250.00
  • National Institutes of Health: $390,308.00
  • National Institutes of Health: $359,270.00
  • National Institutes of Health
  • National Institutes of Health: $193,730.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $283,543.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $321,750.00
  • National Institutes of Health: $359,270.00
  • National Institutes of Health: $382,501.00
  • National Institutes of Health
  • National Institutes of Health: $359,270.00
  • National Institutes of Health: $321,750.00
  • National Institutes of Health: $321,750.00
  • National Institutes of Health: $370,000.00
  • National Institutes of Health: $394,250.00
  • National Institutes of Health: $263,094.00

Fingerprint

Sodium
Heart Failure
Atrial Natriuretic Factor
Kidney
Natriuretic Peptides
Peptides
Renin-Angiotensin System
Neprilysin
Dietary Sodium
Left Ventricular Dysfunction
Hormone Replacement Therapy
Ventricular Dysfunction
Homeostasis
Hydrostatic Pressure
Hormones
Biomarkers
Therapeutics
Up-Regulation
Renin
Canidae

ASJC

  • Medicine(all)