AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 2 549-R553, Copyright © 1994 by American Physiological Society
Increased endothelium-dependent renal vasodilation in cirrhotic rats
J. Garcia-Estan, N. M. Atucha, J. M. Sabio, F. Vargas, T. Quesada and J. C. Romero
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
We have evaluated the renal blood flow (RBF) response of cirrhotic rats to
endothelium-dependent [acetylcholine (ACh)] and -independent [sodium
nitroprusside (NP)] vasodilators. In anesthetized rats, ACh dose
dependently increased RBF, but the response of the cirrhotic rats (n = 6)
was significantly higher than that of the controls (n = 6). NP also
increased RBF in a dose-dependent manner, but there were no differences
between both groups. NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg
i.v.) significantly reduced the responses to ACh in both groups, but those
of the cirrhotic rats were still higher than those of the controls. In
experiments performed in isolated perfused kidneys, preconstricted with
phenylephrine, dose-response curves for ACh and NP were obtained in the
presence of indomethacin. Both ACh and NP decreased renal perfusion
pressure dose dependently, but only the response of the cirrhotic rats (n =
5) to ACh was significantly higher than that of the controls (n = 5).
L-NAME (100 microM) significantly reduced the responses to ACh and
increased those of NP and abolished the differences between groups, except
at the high dose of ACh. These results demonstrate an elevated
endothelium-dependent vasodilator response in the cirrhotic kidney, which
is eliminated by combined prostaglandin and nitric oxide (NO) synthesis
inhibition and suggest that increased intrarenal activity of NO may be
contributing to the renal alterations of liver cirrhosis.
