Role of the kidney in the pathogenesis of hypertension: Time for a neo-Guytonian paradigm or a paradigm shift?

Roger G. Evans, Peter Bie

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29 Citations (Scopus)


The “Guytonian paradigm” places the direct effect of arterial pressure, on renal excretion of salt and water, at the center of long-term control of blood pressure, and thus the pathogenesis of hypertension. It originated in the sixties and remains influential within the field of hypertension research. However, the concept of one central long-term feedback loop, through which arterial pressure is maintained by its influence on renal function, has been questioned. Furthermore, some concepts in the paradigm are undermined by experimental observations. For example, volume retention and increased cardiac output induced by high salt intake do not necessarily lead to increased arterial pressure. Indeed, in multiple models of salt-sensitive hypertension the major abnormality appears to be failure of the vasodilator response to increased cardiac output, seen in salt-resistant animals, rather than an increase in cardiac output itself. There is also evidence that renal control of extracellular fluid volume is driven chiefly by volume-dependent neurohumoral control mechanisms rather than through direct or indirect effects of changes in arterial pressure, compatible with the concept that renal sodium excretion is controlled by parallel actions of different feedback systems, including hormones, reflexes, and renal arterial pressure. Moreover, we still do not fully understand the sequence of events underlying the phenomenon of “whole body autoregulation.” Thus the events by which volume retention may develop to hypertension characterized by increased peripheral resistance remain enigmatic. Finally, by definition, animal models of hypertension are not “essential hypertension;” progress in our understanding of essential hypertension depends on new results on system functions in patients.
Original languageEnglish
Pages (from-to)R217-R229
Number of pages13
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
Publication statusPublished - 1 Feb 2016


  • Arthur Guyton
  • pressure natriuresis
  • Thomas Coleman
  • water and electrolyte homeostasis
  • whole body autoregulation

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