17.6: Endocrine Regulation of Kidney Function

Learning Objectives

By the end of this section, you will be able to:

• Describe how each of the renin–angiotensin mechanism functions in the extrinsic control of GFR
• Describe how each of the following works to regulate reabsorption and secretion, so as to affect urine volume and composition: renin–angiotensin system, aldosterone, and antidiuretic hormone

Several hormones have specific, important roles in regulating kidney function. They act to stimulate or inhibit blood flow. Some of these are endocrine, acting from a distance, whereas others are paracrine, acting locally.

Renin–Angiotensin–Aldosterone

Renin is an enzyme that is produced by the juxtaglomerular (JG) cells of the afferent arteriole at the juxtaglomerular apparatus (JGA). It enzymatically converts angiotensinogen (made by the liver, freely circulating) into angiotensin I. Its release is stimulated by the JGA in response to decreased extracellular fluid (ECF) volume.

Angiotensin-converting enzyme (ACE) is not a hormone but it is functionally important in regulating systemic blood pressure and kidney function. It is produced in the lungs but binds to the surfaces of endothelial cells in the afferent arterioles and glomerulus. It enzymatically converts inactive angiotensin I into active angiotensin II. ACE is important in raising blood pressure. People with high blood pressure are sometimes prescribed ACE inhibitors to lower their blood pressure.

Angiotensin II is a potent vasoconstrictor that plays an immediate role in the regulation of blood pressure. It acts systemically to cause vasoconstriction as well as constriction of both the afferent and efferent arterioles of the glomerulus. In instances of blood loss or dehydration, it reduces both GFR and renal blood flow, thereby limiting fluid loss and preserving blood volume. Its release is usually stimulated by decreases in blood pressure, and so the preservation of adequate blood pressure is its primary role.

Aldosterone, often called the “salt-retaining hormone,” is released from the adrenal cortex in response to angiotensin II or directly in response to increased plasma K⁺. It promotes Na⁺ reabsorption by the nephron, promoting the retention of water. When Na+ is reabsorbed into the blood, it increases the solute concentration of the blood. Water will then follow and be reabsorbed, as water moves towards an area of higher concentration of solutes via osmosis. Aldosterone is also important in regulating K⁺, promoting its excretion. As a result, renin has an immediate effect on blood pressure due to angiotensin II–stimulated vasoconstriction and a prolonged effect through Na⁺ recovery due to aldosterone. At the same time that aldosterone causes increased recovery of Na⁺, it also causes greater loss of K⁺. Progesterone is a steroid that is structurally similar to aldosterone. It binds to the aldosterone receptor and weakly stimulates Na⁺ reabsorption and increased water recovery. This process is unimportant in males due to low levels of circulating progesterone. It may cause increased retention of water during some periods of the menstrual cycle in females when progesterone levels increase.

Figure \(\PageIndex{1}\) Conversion of Angiotensin I to Angiotensin II The enzyme renin converts the pro-enzyme angiotensin I; the lung-derived enzyme ACE converts angiotensin I into active angiotensin II.

Antidiuretic Hormone (ADH)

Diuretics are drugs that can increase water loss by interfering with the recapture of solutes and water from the forming urine. They are often prescribed to lower blood pressure. Coffee, tea, and alcoholic beverages are familiar diuretics. ADH, a hormone released by the posterior pituitary, works to do the exact opposite. It promotes the recovery of water, decreases urine volume, and maintains plasma osmolarity and blood pressure. When stimulated by ADH, the cells of the collecting duct will insert aquaporin channel proteins into their membranes, which as their name suggests, allow water to pass from the collecting duct lumen through the cells and into the interstitial spaces to be recovered by the vasa recta and returned to the blood. This process allows for the recovery of large amounts of water from the filtrate back into the blood. In the absence of ADH, these channels are not inserted, resulting in the excretion of water in the form of dilute urine. Most, if not all, cells of the body contain aquaporin molecules, whose channels are so small that only water can pass. At least 10 types of aquaporins are known in humans, and six of those are found in the kidney. The function of all aquaporins is to allow the movement of water across the lipid-rich, hydrophobic cell membrane (Figure \(\PageIndex{2}\)).

Figure \(\PageIndex{2}\) Aquaporin Water Channel Positive charges inside the channel prevent the leakage of electrolytes across the cell membrane, while allowing water to move due to osmosis.