Nitric oxide enhancement of erythropoietin production in the
isolated perfused rat kidney.
Yoshioka, Kunihiko, and James W. Fisher.
Department of Pharmacology, Tulane University, School of Medicine,
New Orleans, LA
APStracts 2:0156C, 1995.
We have previously reported that nitric oxide (NO) and cyclic
guanosine monophosphate (cGMP) may be involved in the regulation of
erythropoietin (Epo) production in response to hypoxia both in vivo
and in vitro (20). In the present studies, we have used the isolated
perfused rat kidney (IPRK) to assess the role of NO in oxygen sensing
and Epo production. When arterial PO2 was reduced from 100
(normoxemic) to 30 (hypoxemic) mmHg in the perfusate of this system,
perfusate levels of Epo were significantly increased. This hypoxia
-induced increase in Epo production was significantly decreased by the
addition of NG-nitro-L-arginine methyl ester (L-NAME) (1mM) to the
perfusates. Hypoxemic perfusion also produced a significant increase
and L-NAME significantly inhibited this increase in intracellular
cGMP levels in the kidney when compared with normoxemic perfused
kidneys. Quantitative RP-PCR also revealed that hypoxemic perfusion
produced significant increases in Epo messenger RNA levels in the
kidney which was blocked by L-NAME. Our findings further support an
important role of the nitric oxide/cGMP system in hypoxic regulation
of Epo production.
Received 9 January 1995; accepted in final form 16 March 1995.
APS Manuscript Number C17-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.