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Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide

Nature volume 378, pages 65–68 (1995)Cite this article

Abstract

AROUND half of all humans with essential hypertension are resist-ant to salt (blood pressure does not change by more than 5 mm Hg when salt intake is high)1"5, and although various inbred strains of rats display salt-insensitive elevated blood pressure6, a gene defect to account for the phenotype has not been described. Atrial natriuretic peptide (ANP) is released from the heart in response to atrial stretch and is thought to mediate its natriuretic and vaso-relaxant effects through the guanylyl cyclase-A receptor (GC-A)7. Here we report that disruption of the GC-A gene results in chronic elevations of blood pressure in mice on a normal salt diet. Unexpectedly, the blood pressure remains elevated and unchanged in response to either minimal or high salt diets. Aldosterone and ANP concentrations are not affected by the genotype. Therefore, mutations in the GC-A gene could explain some salt-resistant forms of essential hypertension and, coupled with previous work8, further suggest that the GC-A signalling pathway dominates at the level of peripheral resistance, where it can operate independently of ANP.

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Authors and Affiliations

  1. The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75235-9050, USA

    Ichiro Kishimoto, Valerie Mach, Janet Friesen, David L. Garbers & Annie Beuve

  2. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, 75235-9050, USA

    M. James Lopez, Stephen K.-F. Wong, Ichiro Kishimoto, Susan Dubois, Valerie Mach, Janet Friesen, David L. Garbers & Annie Beuve

  3. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, 75235-9050, USA

    M. James Lopez

  4. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, 75235-9050, USA

    Susan Dubois

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Lopez, M., Wong, SF., Kishimoto, I. et al. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature 378, 65–68 (1995). https://doi.org/10.1038/378065a0

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