The long-term goal of the proposed research is to characterize the regulation of renal sodium excretion. The broad objective of the current proposal is to determine the relationship between peritubule capillary dynamics and sodium reabsorption. Our working hypothesis is that increased renal interstitial hydrostatic pressure decreases sodium chloride reabsorption by the loop of Henle. Renal vasodilators with differing characteristics will be used as tools to discern the relationships between physical factors in the peritubular microcirculation and interstitium and subsequent effects on sodium reabsorption. The microcirculation and single nephron reabsorption of sodium will be studied utilizing micropuncture techniques primarily in rats. The specific questions to be addressed are: 1) What is the mechanism for peritubular capillary uptake of reabsorbate in the presence of renal vasodilators? 2) Why do some renal vasodilators increase renal interstitial hydrostatic pressure and sodium excretion while others do not? 3) What tubular site(s) is affected by changes in interstitial hydrostatic pressure mediated by vasodilators? 4) Is there a cause and effect relationship between changes in interstitial hydrostatic pressure and changes in sodium reabsorption? 5) What is the role of washout of the medullary concentration gradient in the natriuresis associated with renal vasodilation? Answers to these questions shold provide an understanding of the relationship between the renal circulation and sodium excretion. Specifically, the role of renal interstitial hydrostatic pressure as an important intrarenal mechanism for the regulation of sodium excretion, such as in the escape from the salt-retaining effects of mineralocorticoids, will be clarified. This is turn should provide a fundamental link in the pathophysiology of diseases characterized by abnormal sodium metabolism such as congestive heart failure and hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL014133-17
Application #
3334739
Study Section
General Medicine B Study Section (GMB)
Project Start
1979-05-01
Project End
1989-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
17
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Khraibi, A A; Taylor, K H; Ramsey, C R et al. (1997) Blockade of cytochrome P-450 epoxygenase pathway attenuates the natriuresis of N(G)-monomethyl-L-arginine infusion in the spontaneously hypertensive rat. J Lab Clin Med 129:330-6
Peng, Y; Ramsey, C R; Knox, F G (1996) Reversal of the antinatriuretic effect of prostaglandin E2 by verapamil in the rat. Kidney Blood Press Res 19:115-20
Haas, J A; Knox, F G (1996) Effect of meclofenamate or ketoconazole on the natriuretic response to increased pressure. J Lab Clin Med 128:202-7
Khraibi, A A (1995) Role of renal nerves in natriuresis of L-NMMA infusion in SHR and WKY rats. Am J Physiol 269:F17-21
Peng, Y; Knox, F G (1995) Comparison of systemic and direct intrarenal angiotensin II blockade on sodium excretion in rats. Am J Physiol 269:F40-6
Lockhart, J C; Larson, T S; Knox, F G (1994) Perfusion pressure and volume status determine the microvascular response of the rat kidney to NG-monomethyl-L-arginine. Circ Res 75:829-35
Brimijoin, S; Hammond, P; Khraibi, A A et al. (1994) Catecholamine release and excretion in rats with immunologically induced preganglionic sympathectomy. J Neurochem 62:2195-204
Khraibi, A A (1994) Inhibition of nitric oxide causes exaggerated natriuresis in spontaneously hypertensive rats. Am J Physiol 266:F762-6
Haas, J A; Lockhart, J C; Larson, T S et al. (1994) Natriuretic response to renal interstitial hydrostatic pressure during angiotensin II blockade. Am J Physiol 266:F117-9
Mimura, Y; Khraibi, A A; Heublein, D M et al. (1994) Acute hypocapnia blunts natriuretic and diuretic effects of atrial natriuretic factor in rats. Am J Physiol 266:R1503-9

Showing the most recent 10 out of 51 publications