The objective of this proposal is to investigate the hypothesis that changes in renal perfusion pressure (RPP) may not be fully transmitted to the renal interstitium in hypertensive as compared with normotensive states, thus resulting in an attenuated pressure natriuresis and diuresis response. The acute and chronic relationship between sodium excretion and RPP is shifted to higher pressure values in many rat models of hypertension. The pressure natriuresis and diuresis response appears to be blunted in hypertension; however, the mechanism(s) responsible for it is not well understood. A method which allows for direct and continuous measurement of renal interstitial hydrostatic pressure (RIHP) in anesthetized rats was developed. A polyethylene (PE) matrix is implanted chronically in the kidney three weeks prior to RIHP measurement. On the day of the experiment, the PE-50 catheter is connected to a Micro Switch transducer and RIHP is measured and recorded directly and continuously in the anesthetized rat. RPP is manipulated by placing an inflatable servo- controlled cuff around the abdominal aorta above both renal arteries. The possibility that directly increasing RIHP in the SHR, by renal interstitial volume expansion (RIVE), might lead to normal acute pressure natriuresis and diuresis responses will be tested. The effect of chronic renal denervation on the relationship between RPP, RIHP, and sodium excretion will be determined in the SHR. In addition, the role of RIHP in the exaggerated natriuresis of SHR to acute saline volume expansion will be determined. Other hypertensive models that will be studies include Dahl salt-sensitive (S) rat, one kidney, one clip (1K1C), and two kidney, one clip (2K1C) hypertensive Sprauge-Dawley (SD) rats. In addition, the control rates of 1K1C (uninephrectomized SD rats) will show these relationships after a reduction in renal mass. The possible role of the renin- angiotensin system (RAS) in causing a shift in these relationships will also be assessed since 1K1C is a RAS-independent, while 2K1C is a RAS- dependent model of hypertension. The results of these experiments will help characterize the relationship between changes in RPP, RIHP, and sodium excretion in various forms of hypertension that have different pathogeneses. Comparisons of these relationships to those obtained before the development of hypertension, and from the appropriate normotensive control rats, will identify the possible role that RIHP may play int he mechanism of attenuated acute pressure natriuresis response in different rate models of 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 #
5R29HL041533-03
Application #
3472381
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Khraibi, A A; Ramsey, C R; Heublein, D M et al. (2001) Role of plasma renin activity and the renal nerves in the natriuresis of L-NMMA infusion in rats. Life Sci 69:1123-31
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
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
Berndt, T J; Khraibi, A A; Knox, F G (1995) Interaction of the renal nerves and prostaglandins on the phosphaturic response to PTH in phosphate-deprived rats. Am J Physiol 268:R731-5
Berndt, T J; Khraibi, A A; Thothathri, V et al. (1994) Effect of increased dietary phosphate intake on dopamine excretion in the presence and absence of the renal nerves. Miner Electrolyte Metab 20:158-62
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
Wei, C M; Kim, C H; Khraibi, A A et al. (1994) Atrial natriuretic peptide and C-type natriuretic peptide in spontaneously hypertensive rats and their vasorelaxing actions in vitro. Hypertension 23:903-7
Khraibi, A A (1994) Inhibition of nitric oxide causes exaggerated natriuresis in spontaneously hypertensive rats. Am J Physiol 266:F762-6
Onsgard-Meyer, M J; Berndt, T J; Khraibi, A A et al. (1994) Phosphaturic effect of parathyroid hormone in the spontaneously hypertensive rat. Am J Physiol 267:R78-83
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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