Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites.
MAP, RPF, GFR, V and UNaV were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal conditions and following the high dose ET. ET induced similar increase in MAP and decrease in RPF and GFR in control and cirrhotic rats. High-dose ET produced a significant reduction in UNaV in control rats (from 2.22 +/- 0.46 to 1.14 +/- 0.28 microEq/min, P less than 0.01). By contrast, it induced marked natriuresis in cirrhotic rats (from 0.76 +/- 0.18 to 2.31 +/- 0.70 microEq/min, P less than 0.05). ET significantly increased aldosterone (control rats: 59.3 +/- 2.2 vs. 85.4 +/- 7.4 ng/dl, P less than 0.025; cirrhotic rats: 115.0 +/- 15.8 vs. 163.9 +/- 30.8, ng/dl, P less than 0.05) and ANP (control rats: 20.1 +/- 3.4 vs. 42.7 +/- 7.7, fmol/ml, P less than 0.025; cirrhotic rats: 107.5 +/- 17.3 vs. 214.2 +/- 41.1, fmol/ml, P less than 0.025) and significantly suppressed PRA (control rats: 2.5 +/- 0.5 vs. 0.2 +/- 0.04, ng/ml.hr, P less than 0.025; cirrhotic rats: 16.6 +/- 2.9 vs. 5.0 +/- 1.1, ng/ml.hr, P less than 0.01) in both groups of animals. These results indicate that ET has marked natriuretic properties in cirrhosis with ascites due to inhibition of tubular sodium reabsorption.
Clària
J
J
Hormonal Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
Jiménez
W
W
Arroyo
V
V
Castro
A
A
Asbert
M
M
Ros
J
J
Rivera
F
F
Rodés
J
J
D000818:Animals; D001201:Ascites / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002251:Carbon Tetrachloride; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects
D016232:Endothelins; D002251:Carbon Tetrachloride