AJP - Renal Physiology, Vol 271, Issue 1 1-F1, Copyright © 1996 by American Physiological Society
Phosphodiesterases (PDEs) hydrolyze the 3' phosphoester bond of the purine 3',5'-cyclic monophosphates, cAMP and cGMP
M. L. Zeidel
Resistance to the natriuretic action of atrial natriuretic peptide (ANP) is
a hallmark of states of pathological sodium retention including congestive
heart failure, cirrhosis of the liver, and nephrotic syndrome. A variety of
mechanisms including reduced delivery of filtrate to ANP-sensitive sites in
the inner medullary collecting duct and diminished receptor density in this
tubular segment have been offered to account for this resistance. Recent
studies in experimental nephrotic syndrome and in liver disease produced by
ligation of the common bile duct in rats suggest that increased activity of
cyclic guanosine 3',5'-monophosphate (cGMP) phosphodiesterase may be an
important mediator of renal resistance to ANP. Such increased enzyme
activity rapidly catabolizes the second messenger cGMP, normally formed
when ANP interacts with its biologically active natriuretic peptide. A
receptors, thereby leading to blunted ANP responsiveness. This increased
phosphodiesterase activity offers a novel approach to the management of
clinical conditions associated with sodium retention and edema formation.
