Stimulation of autocrine platelet--derived growth factor AA-homodimer and transforming growth factor beta in vascular smooth muscle cells.

We have investigated the interrelationship between growth factors and vasoconstrictor peptides in terms of their possible paracrine/autocrine regulation of vascular smooth muscle cell differentiation/proliferation. Responses of quiescent cells from spontaneously hypertensive and Wistar-Kyoto rats to stimulation with a selected number of growth factors- and vasoconstrictor peptides were established (induction of mRNA as well as secretion of immunoreactive peptides). A single exposure of quiescent vascular smooth muscle cells to the vasoconstrictor peptides Angiotensin II and Endothelin-1 (10(-8) M each) resulted in a prolonged induction of platelet- derived growth factor A-chain and transforming growth factor beta transcripts (maximal at 5-6 hrs poststimulatory). The interrelationship between platelet- derived growth factor AA and transforming growth factor beta was investigated in experiments using the pure peptides individually for stimulation of mRNA and peptide secretion. Both growth factors enhanced their own and one anothers transcript expression. The results demonstrated that in spontaneously hypertensive rats, an established animal model of hypertension, the steady state balance of this set of growth factors may be disturbed. Defects involved may be attributable to alterations in the secretory machinery and/or amount of autocrine growth factor produced.