Avp inhibits lps and il-1[beta] stimulated no and cgmp production
via v1 receptor in cultured rat mesangial cells.
Umino, Tetsuo, Eiji Kusano, Shigeaki Muto, Tetsu Akimoto, Satoru
Yanagiba, Shuichi Ono, Morimasa Amemiya, Yasuhiro Ando, Sumiko Homma,
Uichi Ikeda, Kazuyuki Shimada and Yasushi Asano.
Departments of Nephrology and *Cardiology, Jichi Medical School,
Tochigi, 329-0498 JAPAN
APStracts 5:0200F, 1998.
The present study examined how AVP affects on nitric oxide metabolism
in cultured rat glomerular mesangial cells (GMC). GMC was incubated
with test agents and nitrite, intracellular cGMP content, iNOS mRNA
and iNOS protein were analyzed by the Griess method, enzyme
immunoassay, Northern blotting and Western blotting, respectively.
AVP ihibited LPS and IL-1[beta] induced nitrite production in a dose
and time dependent manner with concomitant changes of cGMP contents,
iNOS mRNA and iNOS protein. This inhibition by AVP was reversed by V1
but not OXT receptor antagonist. Inhibition by AVP was also
reproduced on LPS and IFN-[gamma]. PKC inhibitors reversed AVP
inhibition, while PKC activator inhibited nitrite production.
Although dexamethasone and PDTC, an inhibitor of NF-kB, inhibited
nitrite production, further inhibition by AVP was not observed. AVP
did not show further inhibition of nitrite production with
actinomycin D, an inhibitor of transcription, or cycloheximide, an
inhibitor of protein synthesis. In conclusion, AVP inhibits LPS and
IL-1[beta] induced NO production through V1 receptor. The inhibitory
action of AVP involves both activation of PKC and the transcription
of iNOS-mRNA in cultured rat GMC.
Received 27 July 1998; accepted in final form 3 November 1998.
APS Manuscript Number F184-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998