R. Brunkhorst et al., RENAL EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE IN CIRRHOTIC RATS WITH AND WITHOUT CAPTOPRIL PRETREATMENT, Nephron, 64(2), 1993, pp. 275-281
Compared to healthy humans in most patients with cirrhosis and renal s
odium and water retention, effects of atrial natriuretic peptide (ANP)
on sodium and water excretion are reduced. It has been postulated tha
t this impaired response to ANP is caused by renal vasoconstriction, i
nduced by high levels of angiotensin II. To further investigate this i
ssue, we studied renal hemodynamics (glomerular filtration rate, GFR,
single nephron GFR, SNGFR, renal blood flow, RBF) and urinary sodium e
xcretion (UNaV) in rats with CCl4-induced cirrhosis of the liver, befo
re and during ANP infusion. The same parameters were determined in cir
rhotic rats after a 4-day pretreatment with the angiotensin-converting
enzyme (ACE) inhibitor captopril before and during ANP. Results were
compared to those obtained in 2 control groups of healthy rats, one of
them pretreated with captopril. Rats with cirrhosis had a significant
ly reduced GFR, SNGFR, RBF, UNaV and an elevated plasma renin activity
compared to healthy controls. ANP caused a significant rise in UNaV (
+ 198%) but no significant change of GFR, SNGFR and RBF in cirrhotic r
ats. Captopril-pretreated rats with cirrhosis had a significantly high
er RBF (+ 26%) and 24-hour urinary sodium excretion (+ 52%) but no sig
nificant differences in GFR and SNGFR compared to cirrhotic rats witho
ut captopril pretreatment. Administration of ANP to cirrhotic rats pre
treated with captopril resulted in a significant rise in GFR (+ 56%),
SNGFR (+ 42%), RBF(+ 29%) and UNaV(+ 159%) compared to cirrhotic rats
with ANP alone. In healthy rats, there was no additional effect of a c
ombined therapy with captopril and ANP. These results demonstrate that
in cirrhosis of the liver, the renal effects of ANP can be enhanced b
y a concomitant ACE inhibition. This implies that the inadequate effec
t of exogenous ANP in liver cirrhosis may be in part caused by antagon
istic actions between the renin-angiotensin system and ANP at least un
der the condition of high angiotensin II levels.