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 sodium and water retention, effects of atrial natriuretic peptide (ANP) on sodium and water excretion are reduced. It has been postulated that this impaired response to ANP is caused by renal vasoconstriction, induced by high levels of angiotensin II. To further investigate this issue, we studied renal hemodynamics (glomerular filtration rate, GFR, single nephron GFR, SNGFR, renal blood flow, RBF) and urinary sodium excretion (UNaV) in rats with CCl4-induced cirrhosis of the liver, before and during ANP infusion. The same parameters were determined in cirrhotic 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 significantly 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 rats. Captopril-pretreated rats with cirrhosis had a significantly higher RBF (+26%) and 24-hour urinary sodium excretion (+52%) but no significant differences in GFR and SNGFR compared to cirrhotic rats without captopril pretreatment. Administration of ANP to cirrhotic rats pretreated 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 combined therapy with captopril and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
Brunkhorst
R
R
Division of Nephrology, Medizinische Hochschule Hannover, FRG.
Wrenger
E
E
Malcharzik
C
C
Brabant
G
G
Koch
K M
KM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D002251:Carbon Tetrachloride; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects
D009320:Atrial Natriuretic Factor; D002216:Captopril; D002251:Carbon Tetrachloride