The transition from experimental to clinical pharmacology: the renin-angiotensin paradigm

Modern molecular medicine is increasingly bridging the gap between basic research and experimental pharmacology and clinical therapeutics and practical medicine. The challenge in hypertension research is to elucidate the primary, genetic causes of elevated blood pressure. The problems with understanding primary (genetic) hypertension in humans are that (a) several genes are involved in the cardiovascular control mechanisms, (b) the genetics are complex, and (c) environmental factors that act over long spans of time confound the genotype/phenotype relationship individually, within a family, and regionally. Polygenetic diseases such as primary hypertension remain puzzles, which necessitates well-defined experimental models and new strategies in the genetics of human primary hypertension. This article will focus on the advances in molecular genetics of hypertension. Using gene technology it is possible to introduce new, additional genes in normotensive and hypertensive animals. In the mouse, it is possible to delete or mutate specific genes; similar technology is being developed for use in the rat.