AJP - Renal Physiology, Vol 245, Issue 4 521-F529, Copyright © 1983 by American Physiological Society
Renal perfusion in dogs with experimental hepatic cirrhosis: role of prostaglandins
M. Levy, M. J. Wexler and C. Fechner
Increased renal production of prostaglandins are thought to be important
for the maintenance of kidney blood flow in advanced cirrhosis. In alert,
unanesthetized dogs with chronic cirrhosis and ascites, produced by bile
duct ligation, we measured inulin and p-aminohippurate (PAH) clearance
before and after the intravenous administration of 2 mg/kg indomethacin, an
inhibitor of prostaglandin production. Inulin and PAH clearance declined by
42 and 43%, respectively. This decline in renal perfusion was not
associated with changes in blood pressure or cardiac output. If portal
hypertension was prevented by creating an end-side portacaval anastomosis
at the time of bile duct ligation, indomethacin was without effect on renal
perfusion whether or not the dog had ascites. If ascites was completely
mobilized in cirrhotic dogs with portal venous hypertension with the aid of
a LeVeen valve, indomethacin depressed inulin and PAH clearance as usual
during the steady-state period once all ascites had been removed. An
attempt was made to determine some of the factors mediating the apparent
increase in renal prostaglandin synthesis by administering various
pharmacological antagonists. The inhibition of angiotensin effect with
saralasin and the inhibition of kallikrein with aprotinin prevented the
usual indomethacin effect. It is concluded that portal hypertension, but
not a "sick liver per se, in cirrhosis activates the renin-angiotensin
system to both produce renal vasoconstriction and stimulate prostaglandin
synthesis, thereby normalizing renal perfusion. Renal kallikrein also
appears to play a role, probably by augmenting renin release.
