Alan C Pao1. 1. aDivision of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford bVeterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.
Abstract
PURPOSE OF REVIEW: Dr Arthur Guyton hypothesized that the capacity of the kidney to excrete sodium ultimately dictates long-term changes in blood pressure. This model has had a profound influence on our understanding of blood pressure regulation. The goal of this article is to review a selection of classic studies and highlight more recent molecular studies supporting or refuting the Guyton model of blood pressure regulation. RECENT FINDINGS: Molecular characterizations of human disorders of sodium homeostasis and blood pressure, and phenotypic analysis of transgenic mouse models, strongly support the Guytonian view that the kidney plays a central role in blood pressure control. However, recent studies also support the view that primary changes in the vasculature and nervous system significantly contribute to long-term changes in blood pressure. SUMMARY: The findings from provocative studies, particularly those that demonstrate how primary changes in the vasculature alter blood pressure without affecting renal sodium handling, challenge the Guyton model and need to be reconciled with the basic tenets of this model. Future characterization of these exceptions to the Guyton model will be critical in gaining a more complete understanding of the physiology of blood pressure regulation. This path of discovery will undoubtedly lead to new approaches for the diagnosis and treatment of hypertension.
PURPOSE OF REVIEW: Dr Arthur Guyton hypothesized that the capacity of the kidney to excrete sodium ultimately dictates long-term changes in blood pressure. This model has had a profound influence on our understanding of blood pressure regulation. The goal of this article is to review a selection of classic studies and highlight more recent molecular studies supporting or refuting the Guyton model of blood pressure regulation. RECENT FINDINGS: Molecular characterizations of human disorders of sodium homeostasis and blood pressure, and phenotypic analysis of transgenic mouse models, strongly support the Guytonian view that the kidney plays a central role in blood pressure control. However, recent studies also support the view that primary changes in the vasculature and nervous system significantly contribute to long-term changes in blood pressure. SUMMARY: The findings from provocative studies, particularly those that demonstrate how primary changes in the vasculature alter blood pressure without affecting renal sodium handling, challenge the Guyton model and need to be reconciled with the basic tenets of this model. Future characterization of these exceptions to the Guyton model will be critical in gaining a more complete understanding of the physiology of blood pressure regulation. This path of discovery will undoubtedly lead to new approaches for the diagnosis and treatment of hypertension.