RENAL EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE IN CIRRHOTIC RATS WITH AND WITHOUT CAPTOPRIL PRETREATMENT

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.