John M Hamlyn1, Mordecai P Blaustein. 1. Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA. jhamlyn@umaryland.edu
Abstract
PURPOSE OF REVIEW: Endogenous cardiotonic steroids (CTS) exert long-term effects on salt and blood pressure homeostasis. Here we discuss recent observations on mechanisms of salt sensitivity that involve endogenous ouabain and novel pathways in the brain and discuss their possible relationship to arterial and renal function in hypertension. RECENT FINDINGS: Chronic elevation of brain sodium promotes sustained hypertension mediated by central endogenous ouabain and the Na(+) pump α-2 catalytic subunit. The intermediary pressor mechanism in the brain involves aldosterone biosynthesis, activation of mineralocorticoid receptors and increased epithelial sodium channel activity. In the periphery, elevated plasma CTS raise contractility and blood pressure by augmentation of sympathetic nerve responses, increasing arterial Ca(2+) signaling and blunting nitric oxide production in the renal medulla and collecting ducts. SUMMARY: Endogenous ouabain in the brain appears to play a critical role in salt sensitivity and hypertension. In the periphery, the J-shaped relationship of plasma endogenous ouabain in response to short-term changes in salt balance in humans raises the possibility that endogenous ouabain contributes to the increased risk of adverse cardiovascular events associated with both low and high salt intakes.
PURPOSE OF REVIEW: Endogenous cardiotonic steroids (CTS) exert long-term effects on salt and blood pressure homeostasis. Here we discuss recent observations on mechanisms of salt sensitivity that involve endogenous ouabain and novel pathways in the brain and discuss their possible relationship to arterial and renal function in hypertension. RECENT FINDINGS: Chronic elevation of brain sodium promotes sustained hypertension mediated by central endogenous ouabain and the Na(+) pump α-2 catalytic subunit. The intermediary pressor mechanism in the brain involves aldosterone biosynthesis, activation of mineralocorticoid receptors and increased epithelial sodium channel activity. In the periphery, elevated plasma CTS raise contractility and blood pressure by augmentation of sympathetic nerve responses, increasing arterial Ca(2+) signaling and blunting nitric oxide production in the renal medulla and collecting ducts. SUMMARY: Endogenous ouabain in the brain appears to play a critical role in salt sensitivity and hypertension. In the periphery, the J-shaped relationship of plasma endogenous ouabain in response to short-term changes in salt balance in humans raises the possibility that endogenous ouabain contributes to the increased risk of adverse cardiovascular events associated with both low and high salt intakes.
Authors: Hertzel C Gerstein; Michael E Miller; Saul Genuth; Faramarz Ismail-Beigi; John B Buse; David C Goff; Jeffrey L Probstfield; William C Cushman; Henry N Ginsberg; J Thomas Bigger; Richard H Grimm; Robert P Byington; Yves D Rosenberg; William T Friedewald Journal: N Engl J Med Date: 2011-03-03 Impact factor: 91.245
Authors: James W Van Huysse; Iva Dostanic; Jerry B Lingrel; Xiaohong Hou; Hengwei Wu Journal: Am J Physiol Heart Circ Physiol Date: 2011-08-19 Impact factor: 4.733
Authors: R Curtis Morris; Olga Schmidlin; Anthony Sebastian; Masae Tanaka; Theodore W Kurtz Journal: Circulation Date: 2016-03-01 Impact factor: 29.690
Authors: Estela S Estapé; Lorena González-Sepúlveda; Wen Wei; Ingrid Rodríguez-Rivera; Ivette Torres-Negrón Journal: Int Arch Transl Med Date: 2018-09-06