Dynamic aspects of the tubuloglomerular feedback mechanism

Abstract

Tubuloglomerular feedback (TGF) is an important intrarenal regulatory mechanism, which acts to stabilize renal blood flow, GFR, and the tubular flow rate. The anatomical basis for this negative feedback system is the Juxtaglomerular Apparatus (JGA). This is located at the point of contact between the thick ascending limb of the loop of Henle (TAL) and the vascular pole of the glomerulus. The JGA includes the macula densa, a specialized plaque of cells in the TAL thought to be responsible for the sensing step in the feedback mechanism; the mesangial cells, a cushion of cells separating the macula densa from the vascular pole of the glomerulus; and the afferent arteriole, the main effector site for the TGF. An increase in the NaCl concentration at the macula densa elicits a response in the smooth muscle cells of the afferent arteriole increasing the hemodynamic resistance of the preglomerular vasculature. These changes will, through decreases in the GFR and the tubular flow rate, cause a decrease in the NaCl concentration at the macula densa. Thus, the system acts to stabilize the NaCl concentration at the macula densa. The purpose of the present study was to describe the dynamic characteristics of the TGF, and to use this knowledge in elucidating the role of the TGF system in the autoregulation of renal blood flow. Further, by comparing the dynamic characteristics of TGF between hypertensive and normotensive rats, to identify possible alterations in renal function that could play a role in the etiology and pathogenesis of hypertension. Anesthesia and surgery are unavoidable complications in experimental work in animals. It is shown that the anesthetics commonly used in micropuncture experiments in rats have different effects on various aspects of renal function, e.g. GFR, sodium excretion, proximal tubular compliance, and TGF function. It is concluded that the thiobarbiturate inactin, the most used anesthetic, has more detrimental effects on renal function than halothane and other barbiturates. In halothane anesthetized rats, the proximal tubular pressure oscillates with a frequency of 30-50 mHz. The pressure oscillations are associated with oscillations in tubular flow, and the early distal tubular Cl- activity. The possible mechanisms behind the oscillations are discussed. It is concluded that the oscillations appear because of the operation of the TGF system. Although it seems unlikely, it cannot be excluded that a vascular pacemaker is involved in the underlying oscillatory mechanism. To test the hypothesis that the oscillations are caused by the TGF system, a series of dynamic mathematical models of the TGF system have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)