The kidney has the ability to alter its urine flow and sodium excretion in response to changes in renal arterial pressure. Such a relationship between arterial pressure and urinary sodium excretion has remained a critical aspect of many concepts concerning the long term regulation of blood pressure. Several studies have indicated that this mechanism helps to maintain blood pressure at a normal level. A deficient regulation of this relationship between arterial pressure and urinary sodium excretion could result in hypertension. The intrarenal mechanisms responsible for this pressure induced natriuretic responses remain undefined but it has recently been reported that inhibition of nitric oxide synthesis in anesthetized dogs attenuates the sodium excretory responses to changes in renal arterial pressure. In this proposed research, the possible mediatory role of nitric oxide in the phenomenon of pressure-natriuresis will be investigated. In anesthetized dogs, renal excretory responses to changes in renal arterial pressure will be examined during intrarenal administration of nitric oxide synthesis inhibitors as well as nitrovasodilator drugs which release nitric oxide, to examine the definitive role of nitric oxide in the tubular transport of sodium. Total renal blood flow will be measured by electromagnetic flowmetry and the regional blood flow in the kidney will be assessed by single fibre laser- doppler flowmetry. Renal interstitial pressure will be measured with a catheter inserted into the kidney. A renal vascular occluder will be used to reduce renal arterial pressure which will be measured through a needle cannula inserted into the renal artery. Intrarenal administration of drugs will be made through this needle cannula. Nitric oxide measuring electrode will be used to measure directly the intrarenal concentration of NO in the kidney. in addition, nitrite/nitrate concentration in urine and plasma samples will also be measured by a colorimetric method using the nitrate reductase enzymes and griess reagent to assess the level of intrarenal nitric oxide activity. To determine precisely the role of distal tubular sodium transport pathways in mediating natriuretic responses to increases in arterial pressure, renal interstitial pressure, regional blood flow changes as well as intrarenal concentration of nitric oxide will be assessed during intrarenal infusion of pharmacological agents (amiloride, bendroflumethiazide) before and during nitric oxide synthesis inhibition. The result of this study may clarify the mechanisms responsible for this pressure-natriuresis phenomenon and may be helpful in developing effective treatments for hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL051306-02
Application #
2378810
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1996-03-01
Project End
2001-02-28
Budget Start
1997-03-01
Budget End
1998-02-28
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Tulane University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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Evans, Roger G; Majid, Dewan S A; Eppel, Gabriela A (2005) Mechanisms mediating pressure natriuresis: what we know and what we need to find out. Clin Exp Pharmacol Physiol 32:400-9
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Majid, Dewan S A; Nishiyama, Akira (2002) Nitric oxide blockade enhances renal responses to superoxide dismutase inhibition in dogs. Hypertension 39:293-7
Nishiyama, A; Majid, D S; Walker 3rd, M et al. (2001) Renal interstitial atp responses to changes in arterial pressure during alterations in tubuloglomerular feedback activity. Hypertension 37:753-9
Majid, D S; Said, K E; Omoro, S A et al. (2001) Nitric oxide dependency of arterial pressure-induced changes in renal interstitial hydrostatic pressure in dogs. Circ Res 88:347-51
Majid, D S; Navar, L G (2001) Nitric oxide in the control of renal hemodynamics and excretory function. Am J Hypertens 14:74S-82S

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