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Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501-1980
We previously
demonstrated remodeling of large and small arteries in angiotensin
II-treated rats, paralleled by an increased expression of
platelet-derived growth factor (PDGF)-A chain mRNA in large
arteries. Both remodeling and PDGF-A expression were associated with
elevation of blood pressure rather than a direct effect of angiotensin
II. To further delineate the role of PDGF-A and elevated blood
pressure, we assessed the level of PDGF-A and -B mRNA and protein in
the wall of large as well as small arteries in the one-kidney, one-clip
(1K1C) hypertensive rat, a non-renin-dependent model of hypertension.
Fourteen days after renal artery stenosis, the thoracic aorta and both
femoral arteries were collected from 1K1C rats
(n = 8) and uninephrectomized controls
(n = 8) and immediately processed for
morphological measurement, immunohistochemistry, RT-PCR, and Western
blotting. Systolic blood pressure was significantly elevated in
hypertensive rats (202 ± 26 mmHg) compared with control rats (122 ± 7.9 mmHg) and was accompanied by arterial hypertrophy in both
aorta and femoral arteries. The mRNA for PDGF-A chain was increased
threefold in the thoracic aorta (P < 0.05) of 1K1C rats, whereas the message for PDGF-B was not
significantly changed in hypertensive versus control animals. A higher
staining of the intima-media was observed by using an anti-PDGF-A chain
polyclonal antibody on paraffin-embedded sections. Western blot results
indicated an ~2-fold increase in PDGF-A protein in aortic and femoral
wall of the 1K1C rats. The results showed that both the mRNA and
protein for PDGF-A chain are increased and well correlated with the
blood pressure and wall area, suggesting a direct effect of elevated pressure on PDGF synthesis, which, in turn, may affect the onset and
progression of vascular hypertrophy.
hypertension; aorta; femoral artery; platelet-derived growth factors; hypertrophy
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