To clarify whether the growth inhibitors, transforming growth factor-β 1 (TGF-β 1 ), heparin, and interferon-γ (IFN-γ) contribute to the development of vascular hypertrophy in spontaneously hypertensive rats (SHR), the growth of vascular smooth muscle cells (VSMC) was evaluated both for cell numbers over a period of 4 days, and [ 3 H]thymidine incorporation over 24 h. Heparin and IFN-γ inhibited the proliferation of VSMC from SHR and Wistar-Kyoto (WKY) rats. TGF-β 1 enhanced SHR-VSMC proliferation by 16.6 +/- 8.9%; in contrast TGF-β 1 inhibited WKY-VSMC proliferation by 60.5 +/- 7.4%. There was no difference in affinity, number of binding sites, or subtype expression of TGF-β 1 receptor between SHR-VSMC and WKY-VSMC. This evidence suggests that the signal transduction system of TGF-β 1 either the receptor itself or downstream signaling molecules, may be altered in SHR-VSMC versus WKY-VSMC. This abnormal responsiveness to TGF-β 1 is involved in the proliferative characteristics of SHR-VSMC. Therefore, TGF-β 1 could contribute to the development of hypertension or vascular hypertrophy in SHR.