Vol. 277, Issue 1, H318-H323, July 1999
Impairment of EDR by a long-term PDGF treatment in
organ-cultured rabbit mesenteric artery
Hideyuki
Yamawaki1,
Koichi
Sato2,
Masatoshi
Hori1,
Hiroshi
Ozaki1,
Shin-Ichiro
Nakamura3,
Hiroyuki
Nakayama4,
Kunio
Doi4, and
Hideaki
Karaki1
1 Department of Veterinary Pharmacology,
2 Radio Isotope Center,
3 Department of Biomedical
Science, and 4 Department of
Veterinary Pathology, Graduate School of Agriculture and Life Sciences,
University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
Platelet-derived
growth factor (PDGF) has been shown to act chronically on blood vessels
to regulate not only proliferation but also vascular tone. These
effects may be at least partly due to the chronic effect of PDGF on
vascular endothelium. To evaluate this possibility, we examined the
effects of PDGF on the endothelium-dependent relaxation (EDR) and total
RNA for endothelial nitric oxide (NO) synthase (eNOS) using an organ
culture system. In rabbit mesenteric arteries cultured in a serum-free
medium for 1 wk, amplitude of the substance P-induced EDR did not
change, whereas dependency of the EDR on NO (~60.0% vs. 18.9%) and
the total amounts of recoverable eNOS mRNA estimated by RT-PCR were
increased compared with those in freshly isolated arteries. Culture
with PDGF for 1 wk decreased the relaxant effect of substance P and
ionomycin (P < 0.01 compared with
the arteries without PDGF), NO production estimated by bioassay (P < 0.01), and eNOS mRNA level,
whereas the sodium nitroprusside-induced relaxation did not change.
These results suggest that PDGF has a chronic effect on vascular
endothelium to decrease eNOS mRNA and NO production and to impair
NO-dependent EDR.
nitric oxide; endothelial nitric oxide synthase; nitric oxide
bioassay; reverse transcriptase-polymerase chain reaction
