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.
Pressure-Natriuresis: The Key Mechanism of HypertensionAs 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 pressurenatriuresis 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). Pressurenatriuresis is a classic negative feedback control system: when arterial blood pressure increases, renal output of sodium and water increases above intake and blood pressure falls. Guyton et al 4 proposed that this feedback mechanism has infinite gain, that is, it completely restores blood pressure to a "set point" at which sodium and water intake and output are balanced. Renal pressure-natriuresis is, therefore, the dominant mechanism controlling the set point about which blood pressure is regulated, and although there are many other short-term blood pressure regulators, the infinite gain of renal pressure-natriuresis feedback trumps all other subsystems over the long-term. Understanding how the normal set point of pressure-natriuresis rises to support hypertension requires consideration of additional questions of biological explanation.
What Role Does Adaptation by NaturalSelection Play?Evolution by natural selection shapes phenotypes adapte...