REGULATION OF PDGF-A - A POSSIBLE MECHANISM FOR ANGIOTENSIN-II-INDUCED VASCULAR GROWTH

This study was designed to determine the effects of angiotensin II inf usion on structure of conduit and resistance arteries and to see if th e effects correlate with changes in platelet-derived growth factor A c hain (PDGF-A) gene and protein expression. Wistar rats were subcutaneo usly infused by osmotic minipump with either angiotensin II (ANG II) a t 200 ng . kg(-1). min(-1) or physiological saline (control) for 14 da ys. Tail-cuff systolic blood pressure was significantly higher in ANG II compared with control rats beginning the second day of infusion and continuing to the end of 2 wk. Both aorta and external spermatic arte ry (first-order arteriole of the cremaster muscle) developed increased wall-to-lumen ratios in the ANG II rats, but this occurred by hypertr ophy of the wall in the aorta and reduction of the lumen in the arteri ole. Digoxigenin-labeled cRNA probes were used for in situ hybridizati on of vascular sections to identify PDGF-A mRNA. Gene expression of PD GF-A in ANG II rats was upregulated in the hypertrophied aorta and the nonhypertrophied arteriole. With the use of immunocytochemistry techn iques, PDGF-A and proliferating cell nuclear antigen were increased in the aorta but not in the arterioles of ANG II rats compared with cont rol rats. These results suggest that the difference in growth response between the aorta and the arteriole induced by ANG II may lie in post transcriptional modification of PDGF-A mRNA, differential control of t ranslation, or turnover of PDGF-A protein.