This document discusses several autacoids, or locally produced compounds, that have important effects on kidney function and the pharmacology of diuretics. It focuses on three in particular: adenosine, prostaglandins, and urodilatin. Adenosine acts through A1 receptors in the kidney to reduce blood flow and glomerular filtration rate, helping to conserve resources in hypoxic conditions. It also enhances sodium-hydrogen exchanger activity and can be blocked by adenosine receptor antagonists, which have diuretic effects. Prostaglandins contribute significantly to renal physiology and other organ function. They act through G protein-coupled receptors to influence salt and water reabsorption at different neph
This document discusses several autacoids, or locally produced compounds, that have important effects on kidney function and the pharmacology of diuretics. It focuses on three in particular: adenosine, prostaglandins, and urodilatin. Adenosine acts through A1 receptors in the kidney to reduce blood flow and glomerular filtration rate, helping to conserve resources in hypoxic conditions. It also enhances sodium-hydrogen exchanger activity and can be blocked by adenosine receptor antagonists, which have diuretic effects. Prostaglandins contribute significantly to renal physiology and other organ function. They act through G protein-coupled receptors to influence salt and water reabsorption at different neph
This document discusses several autacoids, or locally produced compounds, that have important effects on kidney function and the pharmacology of diuretics. It focuses on three in particular: adenosine, prostaglandins, and urodilatin. Adenosine acts through A1 receptors in the kidney to reduce blood flow and glomerular filtration rate, helping to conserve resources in hypoxic conditions. It also enhances sodium-hydrogen exchanger activity and can be blocked by adenosine receptor antagonists, which have diuretic effects. Prostaglandins contribute significantly to renal physiology and other organ function. They act through G protein-coupled receptors to influence salt and water reabsorption at different neph
This document discusses several autacoids, or locally produced compounds, that have important effects on kidney function and the pharmacology of diuretics. It focuses on three in particular: adenosine, prostaglandins, and urodilatin. Adenosine acts through A1 receptors in the kidney to reduce blood flow and glomerular filtration rate, helping to conserve resources in hypoxic conditions. It also enhances sodium-hydrogen exchanger activity and can be blocked by adenosine receptor antagonists, which have diuretic effects. Prostaglandins contribute significantly to renal physiology and other organ function. They act through G protein-coupled receptors to influence salt and water reabsorption at different neph
urea transporter UT] (UT-A, UTA-1) molecules into the apical
membranes of collecting duct cells in the medulla.
Urea concentration in the medulla plays an important role
maintaining the high osmolarity of the medulla and in the concen- tration of urine. ADH secretion is regulated by serum osmolality and by volume status. A new class of drugs, the vaptans (see Agents That Alter Water Excretion), are ADH antagonists.
RENAL AUTACOIDS
A number of locally produced compounds exhibit physiologic
effects within the kidney and are therefore referred to as autacoids, or paracrine factors. Several of these autacoids (adenosine, the pros- taglandins, and urodilatin) appear to have important effects on the pharmacology of diuretics. Since these effects are complex, they will be treated independently of the individual tubule segments discussed above.
ADENOSINE
Adenosine is an unphosphorylated ribonucleoside whose actions
in the kidney have been intensively studied. As in all tissues, renal adenosine concentrations rise in response to hypoxia and ATP consumption. In most tissues, hypoxia results in compensatory vasodilation and, if cardiac output is sufficient, increased blood flow. The kidney has different requirements because increased blood flow leads to an increase in glomerular filtration rate (GFR) and greater solute delivery to the tubules. This increased delivery would increase tubule work and A}? consumption. In contrast, in the hypoxic kidney, adenosine actually decreases blood flow and GFR. Because the medulla is alvays more hypoxic than the cortex, adenosine increases “.." scatsorption from the reduced flow in the cortex, so that c«!:veiy co medullary segments will be even further reduced.
There are four distinct adenosine receptors (Ay, Ap, Agps
and A), all of which have been found in the kidney. However, probably only one of these (A,) is of importance. The adenosine A, receptor is found on the pre-glomerular afferent arteriole, as well as the PCT and most other tubule segments. Adenosine is known to affect ion transport in the PCT, the medullary TAL, and collecting tubules. In addition, adenosine (via A, receptors on the afferent arteriole) reduces blood flow to the glomerulus (and GFR) and is also the key signaling molecule in the process of tubuloglomerular feedback. Adenosine receptor antagonists have generally been found to block the enhancement of NHE3 activ- ity and thus exhibit diuretic activity (see below). It is particularly interesting that unlike other diuretics that act upstream of the collecting tubules, adenosine antagonists do not cause wasting of K’,
PROSTAGLANDINS
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Prostaglandins contribute importantly to renal physiology and to the function of many other organs (see Chapter 18). Five prosta- glandin subtypes (PGE), PGI,, PGD,, PGF,,, and thromboxane