Role of endogenous angiotensin II in the increased expression of growth factors in vascular smooth muscle cells from spontaneously hypertensive rats

In culture, vascular smooth muscle cells (VSMC) derived from spontaneously hypertensive rats (SHR) show exaggerated growth compared with cells from no rmotensive Wistar-Kyoto (WKY) rats. SHR-derived VSMC express higher levels of transforming growth factor (TGF)-beta1, platelet-derived growth factor ( PDGF) A-chain, and basic fibroblast growth factor (bFGF) mRNAs than cells f rom WKY rats. We have recently observed production of angiotensin II (Ang I I) in homogeneous cultures of VSMC from SHR. In the current study we invest igated the contribution of endogenous Ang II to increased expression of the above-mentioned growth factors in VSMC from SHR. The levels of mRNAs encod ing TGF-beta1, PDGF A-chain, and bFGF were determined by reverse transcript ion-polymerase chain reaction and were much higher in VSMC from SHR than in cells from WKY rats. The basal level of Ang II-like immunoreactivity (LI) in conditioned medium as determined by radioimmunoassay was significantly h igher in VSMC from SHR than in cells from WKY rats. Isoproterenol is known to induce angiotensinogen gene significantly increased Ang II-LI in VSMC fr om both WKY rats and SHR. Isoproterenol also increased angiotensinogen, TGF -beta1, PDGF A-chain, and bFGF mRNAs in VSMC from SHR. An angiotensin-conve rting enzyme inhibitor delapril significantly decreased Ang II-LI in VSMC f rom WKY rats and SHR. Delapril considerably decreased the levels of TGF-bet a1, PDGF A-chain, and bFGF mRNAs in VSMC from SHR. An Ang II type I recepto r antagonist CV11974 decreased the levels of TGF-beta1, PDGF A-chain, and b FGF mRNAs, and the levels of TGF-beta1. PDGF-AA, and bFGF proteins in VSMC from SHR. These findings suggest that increased generation of Ang II is ass ociated with enhanced expression of TGF-beta1, PDGF A-chain, and bFGF. and the increases in the levels of these growth factors by endogenous Ang II ma y contribute to the exaggerated growth of VSMC from SHR.