The focus of the following discussion will be on natriuretic peptides, which are substances produced by the body that act on the kidneys to increase the excretion of NaCl. Among these peptides, the two best understood are atrial natriuretic peptide (ANP), produced and stored by atrial myocytes, and brain natriuretic peptide (BNP), produced and stored by ventricular myocytes. Both peptides are secreted when the heart dilates, promoting the relaxation of vascular smooth muscle and increasing the excretion of NaCl and water by the kidneys. Another related natriuretic peptide produced by the kidneys is urodilatin, which specifically promotes NaCl excretion. In general, these natriuretic peptides counteract the actions of the renin-angiotensin-aldosterone system (RAAS) with regards to renal NaCl and water excretion. The actions of these peptides include: 
1. Vasodilation of the afferent arterioles and vasoconstriction of the efferent arterioles of the glomerulus, leading to an increased glomerular filtration rate (GFR) and filtered amount of NaCl.
2. Inhibition of renin secretion by the afferent arterioles.
3. Inhibition of aldosterone secretion by the glomerulosa cells of the adrenal cortex, achieved through the inhibition of renin secretion by the juxtaglomerular cells and direct inhibition of aldosterone secretion by the glomerulosa cells.
4. Inhibition of NaCl reabsorption by the collecting duct, partially due to reduced levels of aldosterone. The natriuretic peptides increase cyclic guanosine monophosphate (cGMP), which inhibits cation channels in the apical membrane of medullary collecting duct cells, resulting in decreased NaCl reabsorption. They also inhibit antidiuretic hormone (ADH) secretion by the posterior pituitary and its action on the collecting duct, leading to decreased water reabsorption and increased water excretion in the urine. Overall, the net effect of natriuretic peptides is an increased excretion of NaCl and water by the kidneys. However, there is limited evidence regarding the impact of reduced circulating levels of these peptides on NaCl and water excretion. It is important to note that a decrease in extracellular fluid volume (ECFV) stimulates the secretion of ADH, which in turn decreases water excretion and helps restore euvolemia (normal fluid volume). 
To maintain Na+ balance and euvolemia, the amount of NaCl excreted by the kidneys must match the amount ingested. In a euvolemic individual, daily urine NaCl excretion is equivalent to daily NaCl intake. The amount of NaCl excreted by the kidneys can vary greatly. Under conditions of salt restriction, virtually no NaCl appears in the urine, while individuals with high NaCl intake can excrete over 1000 mEq/day of NaCl. The adjustment of renal NaCl excretion occurs over a variable time course (hours to days) and depends on the magnitude of the change in NaCl intake. NaCl transport along the nephron follows a general pattern, with the majority (67%) of filtered Na+ being reabsorbed by the proximal tubule, followed by additional reabsorption (25%) in the thick ascending limb of the loop of Henle, and the remaining reabsorption occurring in the distal tubule and collecting duct.
The body produces a number of substances that act on the kidneys to increase NaCl excretion (see ). Of these, natriuretic peptides produced by the heart and kidneys are best understood and will be the focus of the following discussion.
The heart produces two natriuretic peptides. Atrial myocytes produce and store the peptide hormone ANP, and ventricular myocytes produce and store BNP. Both peptides are secreted when the heart dilates (i.e., during volume expansion, with heart failure), and they relax vascular smooth muscle and promote NaCl and water excretion by the kidneys. The kidneys also produce a related natriuretic peptide termed urodilatin. Its actions are limited to promoting NaCl excretion by the kidneys. In general the actions of these natriuretic peptides as they relate to renal NaCl and water excretion antagonize those of the RAAS. These actions include: 1.
Vasodilation of the afferent and vasoconstriction of the efferent arterioles of the glomerulus. This increases the GFR and the filtered amount of NaCl.
2.
Inhibition of renin secretion by the afferent arterioles.
3.
Inhibition of aldosterone secretion by the glomerulosa cells of the adrenal cortex. This occurs via two mechanisms: (a) inhibition of renin secretion by the juxtaglomerular cells, thereby reducing angiotensin II– induced aldosterone secretion, and (b) direct inhibition of aldosterone secretion by the glomerulosa cells of the adrenal cortex.
4.
Inhibition of NaCl reabsorption by the collecting duct, which is also caused in part by reduced levels of aldosterone. However, natriuretic peptides increase cGMP, which inhibits cation channels in the apical membrane of medullary collecting duct cells and thereby decreases NaCl reabsorption.
CHAPTER 35 Control of Body Fluid Osmolality and Volume 5. Inhibition of AVP secretion by the posterior pituitary and AVP action on the collecting duct. These effects decrease water reabsorption by the collecting duct and thus increase excretion of water in the urine. The net effect of natriuretic peptides is to increase excre tion of NaCl and water by the kidneys. Hypothetically a reduction in circulating levels of these peptides would be expected to decrease NaCl and water excretion, but convincing evidence for this has not been reported.
As discussed previously, a decreased ECFV stimulates AVP secretion by the posterior pituitary. Elevated levels of AVP decrease water excretion by the kidneys, which serves to reestablish euvolemia.
Control of NaCl Excretion During Euvolemia
Maintenance of Na+ balance and therefore euvolemia requires precise matching of the amount of NaCl ingested with the amount excreted from the body. As already noted the kidneys are the major route for NaCl excretion. Accordingly, in a euvolemic individual we can equate daily urine NaCl excretion with daily NaCl intake.
As noted, the amount of NaCl excreted by the kidneys can vary widely. Under conditions of salt restriction (i.e., low-NaCl diet), virtually no NaCl appears in the urine. Conversely, in individuals who ingest large quantities of NaCl, renal NaCl excretion can exceed 1000 mEq/day. The time course for adjustment of renal NaCl excretion varies (hours to days) and depends on the magnitude of the change in NaCl intake. Acclimation to large changes in NaCl intake requires a longer time than acclimation to small changes in intake.
The general features of NaCl transport along the nephron are illustrated in
Fig. 35.11 . Most (67%) of the Na+ filtered by the glomerulus is reabsorbed by the proximal tubule. An additional 25% is reabsorbed by the thick ascending limb of the loop of Henle, and the remainder by the distal tubule and collecting duct.