Acta Physiol Scand 1993, 149, 119-120

Acute renal denervation influences the tubuloglomerular feedback mechanism

J. KURKUS+, C. THORUP, P. MORSING and A. E. G. PERSSON Department of Physiology and Biophysics and * Department of Nephrology, University of Lund, Sweden

The tubuloglomerular feedback mechanism (TGF) is an important regulator of glomerular filtration rate (GFR) (Schnermann & Briggs 1992). A change in GFR influences the rate at which electrolytes and water are excreted and thereby the extracellular fluid volume in the body.

Renal denervation is known to produce natriuresis and diuresis, effects that are ascribed to changes in proximal tubular sodium handling (Dibona & Kopp 1992). Also, earlier studies fail to show any change in GFR due to denervation. Nevertheless, a decreased reabsorption, and thereby increased loop of Henle load of sodium would activate the T G F mechanism and reduce GFR. I t has been described earlier (Takabatake et al. 1990) that renal nerves have no influence on setting of the T G F sensitivity in normal Wistar-Kyoto rats. As resetting of T G F sensitivity is a process requiring some time, the authors wanted to study the effect of unilateral renal denervation (DNX) during a longer time period.

The study was carried out on male Sprague-Dawley rats (Msllegaard, Denmark), anaesthetized with Trap- anal with all necessary surgery for micropuncture

Received 19 May 1993, accepted 24 May 1993. Key words: denervation, juxtaglomerular apparatus,

kidney physiology, micropuncture technique, renal nerves, tubuloglomerular feedback.

Correspondence : A. Erik G. Persson, Department of Physiology and Biophysics, Solvegatan 19, 223 62 Lund, Sweden.

performed (Morsing et al. 1987). The rats were divided into two groups, one control group and one experimental group consisting of animals with acute unilateral renal denervation. The DNX was performed under a dissection microscope, by stripping the left renal artery and vein of its adventitia and then cutting all visible nerve bundles. T G F was characterized, starting two hours after completed surgery in both groups.

The proximal tubular stop flow pressure (P8,), which is a relative measure of the glomerular capillary pressure, was measured upstream to a wax block while the distal nephron was perfused with a Ringer solution at different flow rates (0-40 nl min-'). The tubular flow rate at which 50% of the maximal response was obtained, the turning point (TP), was determined. The T P is a good indicator of the T G F sensitivity in that a low TP indicates an increased sensitivity and a high T P indicates a decreased sensitivity.

The results obtained 120min after surgery and DNX are shown in Table 1 and Figure 1. They show that sensitivity of the TGF mechanism was reset 2 h after acute renal denervation. A reduced sensitivity was indicated by a shift in T P from 19 to 27 nl min-', while AP,, was only slightly reduced. The mean arterial blood pressure, the proximal tubular free flow pressure and P,, were not affected.

The reason why the nerval influence on the TGF mechanism has not been discovered earlier may be due to the fact that resetting of T G F sensitivity needs time (h) to develop. When separate measurements of

Table 1. Tubuloglomerular feedback characteristics in control situation and two hours after acute renal denervation (DNX)

p* pt PS, APSf T P (mmHg) (mmHg) (mmHg) (mmHg) (nl min-')

Control (n = 7) 119 f 2 13.0f0.3 43.0k1.5 9.3fl.O 19 .1kl . l DNX (n = 7) 115+3 14.0k0.3 46.7f 1.7 6.9k0.6 27.0f 1.3*

Values are given as mean f SE. Abbreviations are Pa, mean arterial pressure; P,, proximal tubular pressure; P,,, proximal tubular stop-flow pressure; AP,,, maximal stop flow pressure response and TP, turning point.

* P < 0.05 compared with control.

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T P were made 1 h after DNX, no significant change in sensitivity was found. Thus, the present experi- ments document a possible role for renal nerves in the juxtaglomerular apparatus to reset T G F sensitivity. In this way. by direct nervous influence, T G F control

The study was supported by the Bergvall Foundation, the Crafoord Foundation, the Ingabritt and Arne Lundbergs Foundation, the Swedish Medical Re- search Council and funds from the Medical Faculty, University of Lund.

REFERENCES DIBONA, G. F. & KOPP, U.C. 1992. The neural

control of renal function. In: D.W. Seldin & G. Giebisch (eds) The Kidney, Physiology and Patho- physiology, pp. 1157-1204. Raven Press, New York.

MORSING, P., STENBERG, A., M~LER-SUUR, C. & PERSSON, A.E.G. 1987. Tubuloglomerular feedback in animals with unilateral, partial ureteral occlusion. Kidney Int 32, 212-218.

Schnermann, J. & Briggs, J.P. 1992. Function of the juxtaglomerular apparatus : Control of glomerular hemodynamics and renin secretion. In: D.W. Seldin & G. Giebisch (eds) The Kidney, Physiology and Pathophysiology, pp. 1249-1289. Raven Press, New York.

Takabatake, T., Yasuyuki, U., Katsuroh, 0. & Hattori, N. 1990. Attenuation ofenhanced tubuloglomerular feedback activity in SHR by renal denervation. Am

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