Adaptation, allometry, and hypertension.

Abstract

Essential hypertension is a "disease of civiliza-tion" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories , have been forwarded. We find neither completely successful , and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth W hat causes essential hypertension? Despite almost a century of effort, we still do not know, and in part our problem may be that we are asking the question in the wrong way. Medical scientists are natural reductionists, searching for, and often finding, unifying causes such as toxic exposures, dysfunctional systems, and most recently, defective genes, to explain abnormalities of clinical import. Yet not all diseases can be expected to yield to the reductionist strategy, particularly such common disorders as essential hypertension, which seem most likely to result from dys-regulation of essentially normal physiological systems. This is not to say that relatively simple alterations of fundamental components of the cardiovascular system could not result in hypertension. Indeed, some of the most impressive recent advances in hypertension research describe discrete genetic abnormalities that apparently cause some types of hypertension. 1-2 However, the intrinsic complexity of blood pressure control presents formidable, perhaps insurmountable, theoretical and practical barriers to reductionist analyses. 3 For hypertension and other "diseases of civilization," it has been argued that the standard genetic paradigm based on classic monogenic diseases, in which one gene causes one trait abnormality, is fundamentally flawed and should be replaced by an epigenetic view in which genetic information flows through a complex, highly interactive, flexible network of gene-gene and gene-environment interactions 4 (Fig 1). In and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle , the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of mal...

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