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4 urea transporter UT1 (UT-A, UTA-1) molecules into the apical
: membranes of collecting duct cells in the medulla.
ose oo. 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.
4% RENAL AUTACOIDS
4 A number of locally produced compounds exhibit physiologic
{ effects within the kidney and are therefore referred to as autacoids,
4 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
—— eer ee
Adenosine is an unphosphorylated ribonucleoside whose actions
in the kidney have been intensively studied. As in all tissues, renal
orl adenosine concentrations rise in response to hypoxia and ATP
consumption. In most tissues, hypoxia results in compensatory
vasodilation and, if cardiac output is sifiicient, increased blood
e flow. The kidney has different requirements because increased
r blood flow leads to an increase in zlomeruls: Sleretion vate (GPR)
5 and greater solute delivery to the iubules. This increesed delivery
would increase tubule work and Al? consumption. In contrast,
in the hypoxic kidney, adenosine actually decreases blood flow
and GFR. Because the medulla is always more hypoxic than the
a- cortex, adenosine increases Na’ reabsorption from the reduced
t0 flow in the cortex, so that delivery to medullary segments will be
- even further reduced.
) There are four distinct adenosine receptors (A,, Az. Ad»
c and A), all of which have been found in the kidney. However,
5, probably only one of these (Aj) is of importance. The adenosine
j A, receptor is found on the pre-glomerular afferent arteriole, as
7 well as the PCT and most other tubule segments. {neste
: known to affect ion transport in the PCT, the medullary ,
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 NHES aa
ity and thus exhibit diuretic activity (see below). It is par fl y
interesting that unlike other diuretics that act upstream o a
. collecting tubules, adenosine antagonists do not cause wasting
+
: : of kK’,
i PROSTAGLANDINS
i °)
Prostaglandins contribute importantly to renal p ae: a ea
the function of many other organs (see ee thromboxane
glandin subtypes (PGE, PGI, PGDz, PGFan
ae