Renal blood flow

This chapter is relevant to Section G4(ii) and G4(iii)of the 2023 CICM Primary Syllabus, which expects the exam candidate to "describe the distribution of blood volume and flow in the various regional circulations ... including autoregulation... These include, but not limited to, the cerebral and spinal cord, hepatic and splanchnic, coronary, renal and utero-placental circulations". The renal circulation has come up several times in the past papers:

• Question 2 from the second paper of 2019
• Question 4 from the first paper of 2019
• Question 3 from the second paper of 2015
• Question 11 from the first paper of 2012
• Question 21 from the second paper of 2011
• Question 12 from the second paper of 2008
• Question 6(p.2) from the second paper of 2007

Like with cerebral and hepatic metabolism, it was difficult to find a suitable position for this chapter within the revision structure. Is it renal? Is it circulatory? Ultimately, the author had felt that, unless the discussion veers dangerously close to the topic of glomerular filtration or solute clearance, it would be relatively safe to fit this under the cardiovascular heading. 

In summary:

• Renal vascular anatomy
  • Renal arteries are end-arteries (there is no arterial anastomosis inside the kidney)
  • Unique elements include:
    • Two capillary beds:
      • A high pressure capillary network, being the glomerular capillaries
      • A low pressure capillary network, the peritubular capillaries
    • The resistance of the afferent and efferent arterioles, on either side of the high-pressure glomerular capillaries, is an important mechanism of control for glomerular filtration
• Renal blood flow
  • Total blood flow: 20-25% of cardiac output, or 1000ml/min, or 400ml/100g/min
    • 95% goes to the cortex, 5% goes to the medulla
    • Medullary blood flow must remain low to maintain the urea concentration gradient, to facilitate the concentration of urine
  • Total renal blood is high for reasons of filtration rather than metabolism
  • Total renal oxygen extraction is low (10-15%), consuming about 4ml/100g/min
  • Renal oxygen extraction remains stable as renal blood flow changes, because renal metabolic rate depends on glomerular filtration rate and tubular sodium delivery
• Autoregulation of renal blood flow
  • Renal blood flow remains constant over a MAP range of 75-160 mmHg
  • This regulation is produced by:
    • Myogenic response (50% of the total autoregulatory response)
    • Tubuloglomerular feedback (35%)
    • Other mechanisms involving angiotensin-II and NO (<15%)
  • Intrinsic myogenic mechanisms:
    • Vasoconstriction in response to wall stretch
    • This is a stereotyped vascular smooth muscle response, not unique to the kidney
  • Tubuloglomerular feedback
    • This is a negative feedback loop which decreases renal blood in response to increased sodium delivery to the tubule
    • The mechanism is mediated by ATP and adenosine secreted by macula densa cells, which cause afferent arterolar vasoconstriction
• Sympathetic regulation of renal blood flow
  • Sympathetic tone regulates the range of renal blood flow autoregulation
  • Autoregulation typically maintains stable renal blood flow over a wide range of systemic sympathetic conditions
  • Massive sympathetic stimulus (eg. shock) overrides autoregulation and markedly decreases renal blood flow
  • Glomerula filtration rate is less affected (out of porportion to blood flow) because the efferent arterioles vasoconstrict more than the afferent in response to a sympathetic stimulus.

There is a lot of high-quality material in the peer-reviewed literature, and the CICM exam candidate is spoiled for choice, even if they decide not to pay for anything. Stein (1990) is old, but short, good, and free. Braam et al (2014) is new, good, free, but long. Just (2007) is also new and free, but realistically, no CICM primary exam candidate would ever need as much detail as that.

Renal vascular supply

Each kidney is supplied by a renal artery, which is basically a big muscular artery and a main branch of the aorta. Each is about 4-5 cm in length and 5-10 mm in diameter, with one usually a little bigger than the other. Just before entering the parenchyma, the human renal arteries tend to divide into anterior and posterior main branches, which in turn divide into segmental arteries. Inside the kidney, there is no anastomosis between these arteries, i.e each branch is an end-branch and the ischaemia of one segmental artery will create regional ischaemia in the territory of its distribution (Bertram, 2000).

In summary, the arterial and venous circulation of the kidney can be presented as a sequential list of vessels:

• Renal artery, a branch of the aorta
• Anterior and posterior main branches of the renal artery
• Segmental arteries (large end arteries)
• Interlobar arteries, which enter the renal tissue at the border between the cortex and medulla
• Arcuate arteries, which run an arc-like course between the cortex and medulla
• Cortical radial arteries, which ascend radially from the centre towards the renal capsule
• Afferent arterioles, which supply the glomerulus
• Glomerular capillaries, 
• Efferent arterioles, which drain the glomerulus and descend into the medulla
• Peritubular capillaries, which surround the cortical tubules
• Vasa recta,  the descending and ascending straight vessels which surround the loop of Henle along its path into the renal medulla
• Arcuate veins, into which the ascending vasa recta drain
• Interlobular veins, which collect blood from the arcuate veins
• Renal vein, which drains into the inferior vena cava

The diagrams here are reproduced from the excellent "Structural organisation of the mammalian kidney" by Kriz & Kaissling (1992). In retrospect, one has to admit that the original images did not require the added annotation and childish colouring. But...

The physiological significance of the renal vessels for the filtration function of the kidney is discussed elsewhere. In this vascular-focused chapter, it is probably important to focus on the most unique features of the renal microcirculation:

• The renal circulation has two capillary networks:
  • A high-pressure capillary network, being the glomerular capillaries
  • A low-pressure capillary network, the peritubular capillaries
• The resistance of the afferent and efferent arterioles, on either side of the high-pressure glomerular capillaries, is an important mechanism of control for glomerular filtration

Microcirculation of the renal medulla

Question 21 from the second paper of 2011 asked for some specific details about the microcirculation in the renal medulla, the space where long loops of Henle work to concentrate the urine. Fortunately, two excellent articles are available to describe this system (Pallone et al, 2003, and Zimmerhackl et al, 1985). In short, the medulla derives its blood flow from the glomerular vessels, and its vessels have several unique characteristics. The best way to discuss them is probably sequentially, moving along with the flow of blood.

Structure and function of the medullary blood supply:

• Efferent arterioles drain blood from the glomerulus; 
  • Cortical nephron efferent arterioles branch into peritubular capillaries
  • Juxtaglomerular nephron efferent arterioles branch into vasa recta
• Peritubular capillaries:
  • Thin-walled fenestrated capillaries, similar to systemic capillaries
  • Surround the proximal convoluted tubule and distal convoluted tubule
  • Main role is reabsorption and active secretion of solutes
• Vasa recta:
  • Main role is concentration of urine
  • Descending vasa recta:
    • Thicker walls, more smooth muscle;
    • Mainly involved in countercurrent exchange of water
  • Ascending vasa recta: 
    • Thin-walled fenestrated capillaries, similar to systemic capillaries
    • Mainly involved in reclaiming reabsorbed water from the medulla

Efferent arterioles, which drain the glomerulus, are larger than the afferent arterioles, with more smooth muscle and a thicker endothelium. This makes sense, as the efferent arterioles tend to vasoconstrict more than the afferent ones in response to a sympathetic stimulus, a mechanism which maintains glomerular filtration even as renal blood flow decreases. These efferent arterioles descend out of the juxtaglomerular cortex and enter the medulla, where they each fork into about 30 vasa recta. Efferent arterioles coming out of more superficial cortical nephrons turn into peritubular capillaries.

Peritubular capillaries surround the cortical tubules, and are not seen in the medulla. They surround the proximal and distal convoluted tubule. Unlike the vasa recta, which are mainly concerned with reclaiming water from the tubular ultrafiltrate,  the peritubular capillaries are mainly there for active reabsorption of electrolytes and active secretion of solutes.

Vasa recta,  the descending and ascending straight vessels which surround the loop of Henle along its path into the renal medulla, are long straight vessels which travel alongside the descending limbs of the loop of Henle in bundles.

• Descending vasa recta have thicker walls, mainly because of the increased thickness of vascular smooth muscle and pericytes (i.e. histologically they are clearly arterioles, and not capillaries). They deliver blood to the medulla and act as countercurrent exchangers of fluid with the ascending vasa recta. On their way down, they gradually lose their thickness and smooth muscle, turning into a loose capillary network in the inner medulla, full of fenestrations. These capillaries then coalesce together and joint to form the ascending vasa recta.
• Ascending vasa recta are thin-walled, histologically resembling peritubular and systemic capillaries. These vessels drain reabsorbed fluid from the medulla and return it to the circulation. They are even more fenestrated than the capillaries.

The blood carried by the medullary vasa recta is significantly altered in its composition by the act of being filtered in the glomerulus as well as by the effects of passing through the urea-pickled areas of the medulla. Specifically, the plasma proteins are more concentrated.

Renal blood flow

In total, about 20-25% of the total cardiac output ends up flowing through the kidneys. That ends up being about 400ml/100g tissue/min, or about 1000ml per minute; i.e. approximately eight times more than the brain. This is obviously going to be quite different depending on whose kidneys you measure; for example, Bergström (1959) got results ranging from 660ml/min to 2190ml/min from a group of healthy volunteers. 

Obviously, this blood flow is completely unrelated to renal metabolic activity. In total, the kidneys only extract about 10-15% of the delivered oxygen, and renal venous oxygen saturation is therefore relatively high (~ 85%). From this, one might come to the conclusion that the cells of the kidneys must be constantly surrounded in a luxurious excess of oxygen, but in fact this is not the case. All the blood flow tends to go to the cortex (where the glomeruli are), around 500ml/100g/min or 95% of the total, whereas the medulla receives only 20-100ml/min of blood flow. And the medulla is where all the hard-working tubular cells are, busily sucking all the sodium out of tubular fluid. This is not a cheap process, from the metabolic standpoint, as 99.5% of the filtered sodium needs to be reclaimed, and thus the renal medulla has a very high metabolic activity for its mass - it is only 0.5% of the total body mass, but it uses 7% of the total oxygen. 

As one might expect, with this sort of oxygen consumption, the renal medulla is probably chronically oxygen-poor and has a rather high oxygen extraction ratio. Indeed, Leichtweiss et al (1969) measured a renal medullary pO₂ of around 8-10 mmHg. What's worse is the close proximity of the interlobular vessels and vasa recta in the medulla, allowing oxygen to diffuse from the arterial blood directly into the venous, robbing the deeper medullary tissue. Lastly, renal blood flow to the medulla has to be low, otherwise all those carefully constructed concentration gradients will wash away. In summary, in order to be able to concentrate our urine, we need to keep the renal medulla always at the borders of oxygen starvation.

So, the most energy-expensive thing done by the kidney is the reabsorption of sodium, which occurs in the renal medulla. And the amount of sodium delivered to the kidney is dependent on the glomerular filtration rate, which depends on blood flow. Thus, renal metabolic demand is determined by the blood flow, and not the other way around. In other words, if you perfuse the kidney with less blood, there will be less sodium to pump, and therefore less metabolic fuel required. As the result, renal oxygen extraction does not vary overmuch with different rates of blood flow (Levy, 1960). The consumption of oxygen by the whole kidney under conditions of relatively normal blood flow was about 4ml/100g/min (von Horn et al, 2021) 

Autoregulation of renal blood flow

As blood flow though the kidney is an important determinant of glomerular filtartion and solute clearance, it stands to reason that you would want it to remain stable over a wide range of systemic conditions. This is in fact what is observed. The following autoregulation diagram, a relationship of renal blood flow and systemic arterial pressure, is usually trotted out to support this concept in textbooks:

There are many permutations of this graph, and it is so ubiquitous that authors have stopped referencing it in professional publications. Here are a couple of representative examples from official-sounding sources (Burke et al, 2014 and Ravera et al, 2006):

This graph is probably so incredibly variable and poorly referenced because it does not belong to any single author. The idea that the kidney maintains a stable blood flow in the face of changing perfusion pressure was first discovered in the context of a haemorrhagic shock model by Rein & Rossler (1929),  but then literally hundreds of authors performed thousands of experiments exploring every possible circulatory permutation, and everybody produced some kind of pressure-flow curve. Here, a representative image (selected basically at random) is offered from a paper by Rothe et al (1971). It demonstrates most of the important features.

There is marked variation among textbooks and publishers with regards to how this graph is labelled and presented, with many choosing to use actual flow values instead of relative ones, or systolic arterial pressure instead of the mean. Some (like the author above) do not specify which pressure hey were measuring. The act of memorising any specific pressure values for the purposes of the exam is therefore rendered even more ridiculous. In case one's need for completeness insists on a figure, one could do worse than to borrow from the college examiners, who in their answer to reported that blood flow to the kidneys remains "constant against arterial blood pressures from 75 – 160 mmHg".  Ultimately, the most important feature to label on this graph is a plateau of "normal" flow, which is seen in some normal blood pressure range.

This autoregulation occurs at the level of the afferent arteriole, just before the blood enters the glomerulus. It occurs by three main mechanisms: a rapid myogenic mechanism, a slower mechanism related to the rate of salt delivery to the juxtaglomerular cells (tubuloglomerular feedback) and a third mechanism which is slower yet, and which does not have a particularly satisfying explanation. 

Myogenic renal blood flow autoregulation

This property of renal afferent arterioles is in fact common to virtually every other brand of arteriole, and appears to be an intrinsic property of smooth muscle (in the sense that the endothelium is clearly not necessary for it, as arterioles stripped of their endothelium still do this). In short, when pressure (stretch) on the wall of an arteriole increases, the arteriole constricts in response. This increases the vascular resistance, and therefore the flow remains the same, even though the pressure gradient has changed. This is a very rapid process (from zero to constricted in under 10 seconds) and it contributes about 50% of the total regulatory capacity of the renal vessels. The mechanism, as far as anybody can tell, is related to membrane depolarisation which occurs in response to stretch, but exactly what triggers this and how it happens on a molecular level, nobody is quite sure. Schubert & Mulvany (1999) cover this in more detail than would ever be necessary for exam purposes, and the reader is directed there if they want something more than just a brief overview. 

Regulation of renal blood flow by tubulo-glomerular feedback

Unlike the myogenic response, tubuloglomerular feedback (TGF) is something unique to the kidney. It is described brilliantly by Volker Vallon (2003); without going into excessive detail, this mechanism can be summarised as follows:

• Salt reabsorption from the loop of Henle is an active process
• This process is highly dependent on the amount of salt available, i.e. on the rate of tubular fluid flow
• Increased glomerular blood flow increases the flow of tubular fluid (as it increases glomerular filtration)
• Thus, increased glomerular blood flow increases the amount of salt reabsorbed by the loop of Henle, and this increases the delivery of salt to the macula densa
• Changes in salt concentration are sensed by the macula densa via the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) in its luminal membrane.
• This produces an increase in ATP release from macula densa cells
• The ATP then either activates specific purine receptors on the afferent arteriole, or is converted to adenosine (which then acts on A₁-adenosine receptors).
• The net effect is that increased salt delivery to the nephron results in decreased glomerular blood flow, which decreases salt delivery (i.e. this is a negative feedback mechanism

This mechanism is considerably slower than myogenic regulation. To crudely reconstruct some actual animal data from Just (2007), the timing of these mechanisms is shown below.

As you can see, a third regulatory mechanism is described by some authors, but it is probably not very important (accounting for less than 15% of the total regulatory capacity) and - most importantly - it is usually not mentioned in textbooks and in CICM official SAQ answers. This mechanism can be demonstrated by abolishing tubuloglomerular feedback with frusemide. A slow autoregulatory response is still seen, but it is clearly unrelated to the renal salt delivery. 

Regulation of renal blood flow by humoral factors

The basic mechanisms of renal blood flow autoregulation are in turn influenced by various prevailing neurohormonal winds blowing through the circulatory system. Several soluble mediators change the way renal blood flow is handled. Question 21 from the second paper of 2011 chose to ask about this in a bizarre indirect way, by phrasing the question in terms of oxygen delivery to the medulla, and for some reason a major part of the answer was expected to be devoted to the discussion of the oxygen content of whole blood, which of course the kidney has nothing to do with. 

Navar et al (1996) is probably the best resource to discuss paracrine and endocrine mediators of renal blood flow. In short, the major soluble mediators which affect blood flow are:

• ​​​​Vasoconstrictor stimuli:
  • Angiotensin II: increases filtration fraction by constricting the efferent arteriole, i.e. renal blood flow decreases bu glomerular filtration remains stable
  • Endothelin has the net effect of vasoconstriction, even though it acts as a vasodilator in the renal medulla.
• Vasodilator stimuli:
  • Prostaglandins 
  • Bradykinin 
  • Amino acids
  • Blood glucose

Angiotensin II reduces renal blood flow. This might seem to make sense, as it is the main executive element of the volume-defending RAAS, and to decrease renal blood flow would be a reasonable step if one's aim is to conserve the circulating volume. However, like the effect of sympathetic agonists, angiotensin II seems to decrease renal blood flow more than it decreases the glomerular filtration rate, mainly because it affects the efferent arteriole more than the afferent (Levens et al, 1981). This basically means that the filtration fraction is increased, i.e. a larger proportion of the renal blood flow is transformed into ultrafiltrate at the glomerulus. Therefore, angiotensin II in fact acts as a blood flow redistributor, keeping renal function stable in the face of systemic volume changes which prioritise the perfusion of more vital organs.

When ACE is inhibited, there is less angiotensin-II around, which means the efferent arteriole is spared this selective vasoconstriction, and glomerular filtration decreases in proportion to renal blood flow, which means ACE-treated patients who are hypotensive or volume-depleted may develop a greater degree of renal dysfunction (Hricic et al, 1990). In this way, ACE-inhibitors are not intrinsically nephrotoxic, but behave as such when given to a haemodynamically vulnerable patient.

Endothelin is a renal cortical vasoconstrictor which selectively decreases cortical blood flow while simultaneously increasing medullary blood flow (Gurbanov et al, 1996). Specifically, endothelin-1 seems to be the most important from the perspective of renal haemodynamics. Guan & Inscho (2011) were the best resource for this obscure topic, as it was the "renal effects" chapter from a whole book dedicated to endothelin. Without going into excessive detail, the effects of endothelin can be summarised as vasoconstrictive (via stimulation of ET_A receptors on vascular smooth muscle) or vasodilatory (via stimulation of ET_B receptors on vascular endothelium). In the kidney, the differential expression of endothelin receptors produces this variation in effect: the number of ET_B receptors in the medullary blood vessels is about four times greater in the renal medulla, as compared to the cortex.  However, the overall net effect of an endothelin infusion ultimately ends up being the cortical vasoconstriction and decreased renal perfusion because the cortex dominates renal blood flow. 

Prostaglandin and bradykinin act as renal vasodilators.  In fact all sorts of eicosanoids are involved in renal blood flow regulation (Imig et al, 2000), and they can be demonstrated to have either vasoconstricting or vasodilating effects, depending on the prevailing experimental circumstances.  In spite of this variability, PGE₂ is generally seen to vasodilate the afferent arteriole. PGE₂ therefore increases blood flow to the glomerulus and increases glomerular filtration. From this, it follows logically that the inhibition of PGE₂ synthesis (eg. by NSAIDS) should decrease glomerular filtration, and that is indeed what we see. Unfortunately, most accounts of this (eg. Navar et al, 1996) tend to give a lot of detail about what happens without explaining why it is necessary, or what role it plays in renal blood flow regulation. Kim (2008) opines that this is a counterregulatory mechanism designed to maintain renal blood flow when circulating blood volume is low, but this does not make very much sense, as high renal blood flow is not what you want if you are trying to conserve the circulating blood volume.

Protein ingestion and IV amino acids increase renal blood flow, mainly by acting as renal vasodilators. This was well demonstrated by Thomas Hostetter (1986), who fed ten healthy volunteers 3.5g/kg of lean steak and observed that their average GFR increased by 28% for three whole hours after the meal. The change in GFR was entirely due to a significant fall in renal vascular resistance. Tolins & Raij (1991) explored the theory that this is mediated by nitric oxide (it certainly appears to be inhibited by nitric oxide synthesis inhibitors). The underlying mechanism appears to be a modulation of L-arginine transport into the cells; once inside L-arginine then acts as the substrate for NO production, which leads to vasodilation (Kakoki et al, 2006)

Glucose increases renal blood flow by acting as a renal vasodilator. Kasiske et al (1985) confirmed that (at least in disembodied rat kidneys) the infusion of hyperglycaemic blood (about 17 mmol/L glucose) produced an 8-10% drop in renal vascular resistance, a phenomenon they attributed to some kind of prostaglandin-mediated process. The proposed mechanism is the increased formation of diacylglycerol (DAG) from glucose, which acts as a second messenger for many systems but most significantly for protein kinase C, which regulates phospholipase A₂ activity. Phospholipase A₂, as you might remember, is the enzyme responsible for the production of arachidonic acid, the precursor molecule for all eicosanoids. Larkins & Dunlop (1992) blamed this mechanism for the glomerular hyper-perfusion seen in the early stages of diabetic nephropathy.

Effect of sympathetic innervation and circulating catecholamines

The autonomic nervous system innervates and controls the circulation of the kidney in way which is regulatory but not autoregulatory, in the sense that this mechanism does not respond to changes in pressure to keep flow stable. Instead, blood flow to the kidneys is intentionally increased or decreased by this control system. Much better reviews of this topic exist in the literature (eg. Johns et al, 2011).

Sympathetic innervation of the kidney: The vascular structures of the kidney are innervated by sympathetic fibres arising from around T11-L3. Those preganglionic fibers then pass to ganglia, which can be highly variable between individuals - paravertebral, prevertebral, aorticorenal, splanchnic, celiac and superior mesenteric ganglia are all legitimate possibilities, and there is no predictable "spinal level". To make things more complicated, each kidney get innervated by a different level and group of ganglia.  From there, postganglionic sympathetic fibres enter the kidney along with the renal artery, and divide into a network of single fibres which penetrates into the cortex and medulla. Barajas et al (1992) tracked them patiently to their destinations, and found sympathetic nerve endings at multiple sites, including the obvious ones (afferent and efferent arterioles) as well as surprising ones (eg. the granular cells of the juxtaglomerular apparatus, segments of tubule, etc). On closer inspection, these nerve endings are full of noradrenaline.

The effect of stable sympathetic tone: Under normal circumstances, with a nice calm autonomic nervous system, whatever little influence the sympathetic nerves exert ends up being hidden under the blanket of renal myogenic and tubuloglomerular autoregulation. You never really see it. However, even though their effect is subtle, it is clearly a significant influence. When Kompanowska‐Jezierska et al (2001) denervated some rat kidneys, cortical blood flow increased by 25%, illustrating the magnitude of the normal resting sympathetic tone. 

The effect of activating renal sympathetic fibres: When the autonomic nervous system is enraged by some powerful stimulus (for example, a shock state, or a heinously rude colleague), several effects are produced:

• Vasoconstriction of renal vessels 
• Increased sodium and water reabsorption at the tubule
• Increased renin release from the juxtaglomerular cells

The renal vasoconstriction, previously quiet in the background, now becomes much more vigorous. It does not so much override renal autoregulation of blood flow, but rather changes the shape of the autoregulation curve. Here, a graph which borrows from Stadlbauer et al (2008) and Persson (1990) illustrates this concept:

This probably makes sense in the context of a whole-body response to something haemorrhagic. The defence of the circulating volume also necessarily includes not wasting blood on perfusing the kidney. In fact it would be nice if they regulated their own blood flow in a way which spares more blood for the rest of the organism.

How low can you go? The CICM exam answer mentions 10% as the minimum to which the sympathetically vasoconstricted renal blood flow could drop. That may be a theoretical figure, and it is impossible to track down where it came from, but it appears plausible. When Dibona & Sawin (1999) tortured some kidneys with electrical shocks, they ended up generating this graph, which clearly shows that renal blood flow can drop to below 70% with enough stimulation. 

Conceivably, one could increase the sympathetic stimulation and generate even more vasoconstriction. Where would it end? CICM examiners mention 10%, but that seems like a fairly arbitrary place to stop. Surely, the minimum flow through any vessel is actually zero, at least theoretically. Of course, in bedside practice, you will never see this sort of thing in any clinical scenario involving a real living patient, but this is Deranged Physiology. When Spencer et al (1954) injected a 3µg bolus of noradrenaline directly into the exposed renal arteries of a dog, zero flow is exactly what they got:

The effect of sympathetic activation on glomerular filtration is often minimal, at least at moderate levels of activation. From the abovementioned graph, one might assume that decreased renal blood flow would lead to proportionally decreased glomerular filtration. However, it does not. Or at least the decrease in glomerular filtration is not as great as the decrease in renal blood flow. This is because the efferent tubule constricts much more than the afferent, forcing more blood through the glomerulus even as renal blood flow decreases. The range of tolerate stimulus is surprisingly large.  Mills et al (1960) funnelled sympathomimetic drugs into dogs and observed that, unless there was enough vasoconstrictor on board to crank the blood pressure up by 40%, the glomerular filtration rate remained essentially unchanged.

The effect of tubuloglomerular feedback sounds like it would be opposed to the effect of sympathetic stimulation on glomerular filtration, which makes no logical sense for the survival of the organism. By this stage the attentive reader would have noted that the sympathetic decrease in renal blood flow would surely produce decreased salt delivery to the macula densa. Surely, this would then result in afferent arteriolar vasodilation, preserving GFR and maintaining a good urine output? Yes, it would be correct to view this as a conflict, as tubuloglomerular feedback would under these circumstances be expected to oppose the totally sensible autonomic attempts to preserve extracellular volume. Fortunately, afferent arterioles do not dilate very much in the presence of neurohormonal volume defenders. Specifically, angiotensin II  modulates the reactivity of the TGF mechanism, decreasing the reactivity of the afferent arteriole in response to adenosine. The result is a progressive loss of tubuloglomerular feedback reactivity in response to progressive volume loss. With mild volume changes, which result in only minimal neurohormonal response, the tubuloglomerular feedback and myogenic autoregulation remain the dominant mechanisms.