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 investigate the nephron site(s) and mechanisms involved in the natriuresis following elevation of renal perfusion pressure. Our working hypothesis is that transmission of pressure to the renal interstitium activates """"""""interstitial baroreceptors""""""""--medullary interstitia cells. Medullary interstitial cells respond with increases in synthesis of prostaglandins leading to decreases in tubular sodium reabsorption. In addition to changes in renal perfusion pressure, a polyethylene matrix, which is chronically implanted in the renal interstitium of the rat, will be used as a tool to directly increase renal interstitial hydrostatic pressure. The in vivo relationship between hydrostatic pressure in the peritubular microcirculation, interstitium, and subsequent effects on sodium reabsorption will be studied utilizing micropuncture techniques. The in vitro relationship between hydrostatic pressure and prostaglandin production will be studied by measuring the rate of prostaglandin synthesis in medullary tissue slices subjected to different levels of pressure. The specific questions to be addressed are: 1) What is the mechanism for transmission of changes in perfusion pressure to the renal interstitium? 2) What is the link between increases in renal interstitial pressure and increase in prostaglandin synthesis? 3) What is the role of prostaglandins in the decrease of tubular sodium reabsorption following increases in renal interstitial hydrostatic pressure? 4) Is renal sympathetic tone necessary to demonstrate an effect of prostaglandin on sodium reabsorption? 5) What is the interaction of angiotensin II and prostaglandins in the pressure natriuresis phenomenon? Answers to these questions should provide an understanding of mechanisms underlying the relationship between renal perfusion pressure and sodium excretion which in turn are fundamental to the pathogenesis of arterial hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL014133-21
Application #
3334742
Study Section
General Medicine B Study Section (GMB)
Project Start
1969-05-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
21
Fiscal Year
1991
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

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