The Mosaic Theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension

More than 60 years ago, Dr. Irvine Page proposed the Mosaic Theory of hypertension, which states that many factors, including genetics, environment, adaptive, neural, mechanical, and hormonal perturbations interdigitate to raise blood pressure. In the past two decades, it has become clear that common molecular and cellular events in various organs underlie many features of the Mosaic Theory. Two of these are the production of reactive oxygen species and inflammation. These factors increase neuronal firing in specific brain centers, increase sympathetic outflow, alter vascular tone and morphology, and promote sodium retention in the kidney. Moreover, factors such as genetics and environment contribute to oxidant generation and inflammation. Other common cellular signals, including calcium signaling and endoplasmic reticulum stress are similarly perturbed in different cells in hypertension and contribute to components of Page’s theory. Thus, Page’s Mosaic Theory formed a framework for future studies of molecular and cellular signals in the context of hypertension, and has greatly aided our understanding of this complex disease.