Hypertension and atherosclerosis.

Membrane phospholipase C (PLC) activation is induced by the interaction of numerous vasoactive hormones and growth factors with their receptors. Two products are liberated: inositol triphosphate (IP3) and diacyglycerol (DG). The first product liberates intracellular calcium from its stores in the sarcoplasmic reticulum and the second one activates a phosphokinase, which triggers a transmembrane Na+/H+ exchange. A cascade of metabolic events secondary to these chemical changes impinges on the expression of nuclear proto-oncogenes, which determines cell growth. Studies conducted in spontaneously hypertensive rats (SHRs) have shown that PLC is hyperreactive to various agonists and that the phenomenon is present within a variety of cells, fibroblasts, platelets, and myocytes. Therefore, it is likely that hypertension in SHRs is characterized by a diffuse and intrinsic cellular defect that cannot be considered a consequence of the hemodynamic changes of hypertension. On the one hand, enhanced intracellular calcium mobilization may play a role in arterial tone and contraction whereas, on the other hand, enhanced activation of proto-oncogenes, myc, fos, and jun, may be involved in the mechanisms of arteriosclerosis. The pattern of an evolution towards arterial cell proliferation with acquisition of a secretory phenotype with collagen production was indeed observed in cultured cells from the arterial wall.