Evolution and Hypertension

Abstract

Evolution by natural selection is the supreme organizing principle of biology, but it has not been widely applied in medicine.1 Medicine has historically been concerned with mechanistic, or “proximate,” answers to questions of how diseases develop and cause pathology. In contrast, evolutionary, or “ultimate,” questions, frequently ask “why” structures or functions are as they are.2 A full explanation of a disease should ideally address both, and what follows is a review of aspects of proximate and evolutionary thinking in hypertension. As animals evolved, body size increased, and delivery of nutrients to cells came to exceed the range of diffusion. Simple systems capable of supporting cellular metabolism arose, and natural selection went on to shape our staggeringly complex, highly integrated cardiovascular system. Contemporary cardiovascular research is almost exclusively concerned with detailed descriptions of the proximate features of cardiovascular function and structure, and we now understand many aspects in exquisite detail. Blood pressure, however, cannot be reduced to the individual elements of the circulation. It is a function of all of them acting in concert; it is an emergent property of the entire system. All hierarchically organized biological systems have higher-order emergent functions that depend on, but are not predictable from, the structures and functions of lower levels,3 and because emergent properties are lost when a system is disaggregated, integrative physiology is critical to understanding blood pressure regulation. The most comprehensive description of cardiovascular system physiology and blood pressure control is the systems analysis mathematical model developed by Guyton et al,4 which proposes renal pressure-natriuresis as the dominant regulator of blood pressure. The relationship of chronic pressure-natriuresis to the regulation of blood pressure level has been the focus of a great deal of research, and we now understand some of the regulatory mechanisms (reviewed in Reference 5). Pressure-natriuresis …