PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries.
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 approximately 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.
Dobrian
A
A
Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501-1980, USA.
Wade
S S
SS
Prewitt
R L
RL
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology*; D015153:Blotting, Western; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A