The tubuloglomerular feedback mechanism is the second mechanism responsible for autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). This mechanism involves a feedback loop in which changes in GFR lead to alterations in the concentration of NaCl in the tubular fluid. The macula densa cells of the juxtaglomerular apparatus sense these changes and convert them into signals that affect the resistance of the afferent arteriole and subsequently the GFR. When GFR increases, more NaCl enters the macula densa cells, leading to the production and release of adenosine triphosphate (ATP) and adenosine. This results in vasoconstriction of the afferent arteriole and normalization of GFR. Conversely, when GFR and NaCl concentration in the tubular fluid decrease, less NaCl enters the macula densa cells, causing a decrease in ATP and adenosine production and release. This leads to afferent arteriolar vasodilation and restoration of GFR to normal levels. Nitric oxide (NO), produced by the macula densa, attenuates tubuloglomerular feedback, while angiotensin II enhances it. The macula densa may release both vasoconstrictors (ATP and adenosine) and a vasodilator (NO), which counteract each other's actions at the level of the afferent arteriole, ensuring precise control over tubuloglomerular feedback. The macula densa also plays a role in controlling renin secretion by granular cells of the afferent arteriole. Autoregulation of GFR and RBF is crucial in maintaining relatively constant levels of these parameters despite changes in arterial pressure. This prevents sudden changes in urinary excretion of fluid and solutes, which could disrupt fluid and electrolyte balance. It is important to note that autoregulation is absent when arterial pressure is below 90 mm Hg.
The second mechanism responsible for autoregulation of GFR and RBF is the [NaCl]-dependent mechanism known as tubuloglomerular feedback. This mechanism involves a feedback loop in which a change in GFR leads to alteration in the concentration of NaCl in tubular fluid, which is sensed by the macula densa of the juxtaglomerular apparatus and converted into signals that affect afferent arteriolar resistance and thus the GFR (Fig. 33.19 ). For example, when the GFR increases and causes [NaCl] in tubular fluid in the loop of Henle to rise, more NaCl enters the macula densa cells in this segment (Fig. 33.20 ). This leads to an increase in formation and release of adenosine triphosphate (ATP) and adenosine (a metabolite of ATP) by macula densa cells, which causes vasoconstriction of the afferent arteriole and normalization of GFR. In contrast, when GFR and [NaCl] in tubule fluid decrease, less NaCl enters the macula densa cells, and both ATP and adenosine • Fig. 33.19 Tubuloglomerular feedback. An increase in GFR (1) increases [NaCl] in tubule fluid in the loop of Henle (2). The increase in [NaCl] is sensed by the macula densa and converted to a signal (3) that increases the resistance of the afferent arteriole (RA) (4), which decreases GFR. A decrease in GFR has the opposite effects. (Modified from Cogan MG. Fluid and Electrolytes: Physiology and Pathophysiology. Norwalk, CT: Appleton & Lange; 1991.) production and release decline. The fall in [ATP] and [adenosine] results in afferent arteriolar vasodilation, which returns GFR to normal. NO, a vasodilator produced by the macula densa, attenuates tubuloglomerular feedback, whereas angiotensin II enhances tubuloglomerular feedback. Thus the macula densa may release both vasoconstrictors (e.g., ATP and adenosine) and a vasodilator (e.g., NO) that oppose each other’s action at the level of the afferent arteriole. Production plus release of either vasoconstrictors or vasodilators ensures exquisite control over tubuloglomerular feedback.
Fig. 33.20 also illustrates the role of the macula densa in controlling renin secretion by granular cells of the afferent arteriole. This aspect of function of the juxtaglomerular apparatus is considered in detail in
Because animals engage in many activities that can change arterial blood pressure, mechanisms that maintain RBF and GFR relatively constant despite changes in arterial pressure are highly desirable. If GFR and RBF were to rise or fall suddenly in proportion to changes in blood pressure, urinary excretion of fluid and solute would also change suddenly. Such changes in excretion of water and solutes without comparable changes in intake would alter fluid and electrolyte balance (the reason for which is discussed in ). Accordingly, autoregulation of GFR and RBF provides an effective means for uncoupling renal function from arterial pressure, and it ensures that fluid and solute excretion remain relatively constant.
Three points concerning autoregulation should be noted: 1. Autoregulation is absent when arterial pressure is less than 90 mm Hg.