Vasoactive Peptides and Growth Factors in the Pathophysiology of Hypertension

A hallmark of vascular disease is the inappropriate proliferative and synthetic behavior of smooth muscle cells. This phenotypically immature behavior arises as a consequence of the myocytes undergoing conversion from a contractile to proliferative/secretory cell type. The stimulus invoked for this dedifferentiative process has been, until recently, endothelial desquamation and subsequent acute exposure of the smooth muscle cells to platelet-derived mitogens. Pathogenic conversion of myocytes occurs even in the absence of damage to the endothelium, however, and therefore normal components of blood vessels are implicit in this process. These include vasoconstrictor and growth factor peptides, as well as extracellular matrix molecules and associated compounds such as low-density lipoproteins. In vitro experimentation has indicated a number of compounds that, individually, are only mild stimulators of smooth muscle proliferative metabolism but which combine synergistically to induce robust responses. The enhanced proliferative metabolism exhibited by smooth muscle cells derived from the vessels of hypertensive animals, may arise as a consequence of their response to stimulation and/or to perturbation of the mechanisms involved in the inhibition of growth. In vitro experimental models such as the co-culture of smooth muscle and endothelial cells will facilitate definition of the influence of the endothelium on the processes that lead to smooth muscle conversion and modulated gene expression.