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Cited by 82Sodium Intake and HealthBlood Pressure and Hypertension StudiesNitric Oxide and Endothelin Effects

Salt Sensitivity in Blacks: Evidence That the Initial Pressor Effect of NaCl Involves Inhibition of Vasodilatation by Asymmetrical Dimethylarginine

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Schmidlin, Olga, Forman, Alex, Leone, Anna, Sebastian, Anthony, Morris, R. Curtis·2011·Hypertension
DOI 10.1161/hypertensionaha.111.170175
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Abstract

In healthy, mostly normotensive blacks, 19 salt-sensitive (SS) and 18 salt-resistant (SR), we tested the hypothesis that, in SS subjects, dietary NaCl loading induces its initial pressor effect by inducing a normal increase of cardiac output, while failing to induce a normal pressor-offsetting vasodilatation, consequent to its inhibition by asymmetrical dimethylarginine that is abnormally increased by NaCl. In SS and SR subjects, dietary NaCl loading, 250 from 30 mmol/d, over a 7-day period, induced similar, immediate increases in external Na + balance (by day 2, ≈360 mmol), plasma volume (+11%), and cardiac output (+8%). In SR subjects, from day 1, transient decreases occurred in both systemic vascular resistance (nadir: −13%, day 2) and mean arterial pressure (nadir: −5%, day 2). In SS subjects, systemic vascular resistance did not change over days 1 to 3, whereas mean arterial pressure increased progressively after day 1, ultimately by 10 mm Hg. Failure of systemic vascular resistance to normally decrease, while cardiac output normally increased, accounted for salt's initial pressor effect in the SS subjects. In SS subjects, baseline plasma levels of asymmetrical dimethylarginine (0.76 μmol/L) and symmetrical dimethylarginine (0.60 μmol/L), which does not affect vasodilatation, approximated those in SR subjects. In SS but not SR subjects, NaCl loading induced increases in asymmetrical dimethylarginine on both days 2 (+38%, median) and 7 (+14%, median). Symmetrical dimethylarginine changed in neither group. For all of the subjects combined, changes in asymmetrical dimethylarginine on day 2 predicted changes in systemic vascular resistance ( R =0.751; P <0.001) and mean arterial pressure ( R =0.527; P =0.006) on day 2 and similarly on day 7. These observations support the hypothesis tested.

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  • Schmidlin et al found that when normal subjects moved from a very low salt diet to a high salt diet, mean arterial pressure fell by 5% during the first 12 to 48 hours and then returned to baseline by day 5.

    “In the study of Schmidlin et al,15 switching from a very low salt diet to a high salt diet induced a 5% decrease in mean arterial pressure during the first 12 to 48 hours of salt loading, followed by a return of mean arterial pressure to baseline by the 5th day of salt loading (Figure 3).”

    From Testing Computer Models Predicting Human Responses to a High-Salt Diet: Implications for Understanding Mechanisms of Salt-Sensitive Hypertension (2018) · cites this paper as [15]

    The Hemodynamic Effects of LS and HS Diets section reports a 5% fall in mean arterial pressure within 9 hours of salt loading in salt-resistant subjects, persisting through day 4 before returning toward low-salt levels. The claim leaves out that this response was specific to the salt-resistant group: mean arterial pressure instead rose in salt-sensitive subjects. The text also does not establish an exact return to baseline by day 5. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • In light of the current studies and previous animal and human experiments, the use of these models by Guyton and colleagues to reorient understanding of hypertension causes appears to have been overreaching.

    “However, in light of the results of the current studies with the 1972 Guyton model and its derivatives, together with those of previous experimental studies in animals47–50 and humans,15, 18, 51, 52 the use of the models by Guyton and colleagues to “reorient understanding” of the causes of hypertension appears to have been overreaching.”

    From Testing Computer Models Predicting Human Responses to a High-Salt Diet: Implications for Understanding Mechanisms of Salt-Sensitive Hypertension (2018) · cites this paper as [15]

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Research works printed but not linked: 1

  1. [36]36. Morris RC, Jr., Sebastian A, Forman A, Tanaka M, Schmidlin O. Nor- motensive salt-sensitivity: effects of race and dietary potassium. Hyper- tension. 1999;33:18 -23.

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Authors
Schmidlin, O., Forman, A., Leone, A., Sebastian, A., & Morris, R. C.
Affiliations
  • University of California, San Francisco (US)
  • From the University of California, San Francisco, Department of Medicine, Division of Nephrology (O.S., A.F., A.S., R.C.M.), San Francisco, CA; OXONON BioAnalysis (A.L.), Emeryville, CA.
ORCID
Leone, Anna
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-09
Volume
58
Issue
3
Pages
380-385
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.111.170175
OpenAlex
W2132229867
Semantic Scholar
75dcd7688693fc8a484f69eacd23c50fbf7994ba
Cited by
82
References
77
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 4 · 2019: 2 · 2018: 10 · 2017: 11 · 2016: 10 · 2015: 4 · 2014: 4 · 2013: 2 · 2012: 1
FWCI
2.36
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • University of California, San Francisco
  • National Center for Research Resources
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
salt sensitivity, systemic vascular resistance, mean arterial pressure, cardiac output, asymmetric dimethylarginine, symmetric dimethylarginine, vasodilation, sodium balance, plasma volume, Black people
MeSH terms
Adult, Arginine, Black or African American, Blood Pressure, Dose-Response Relationship, Drug, Female, Hemodynamics, Humans, Hypertension, Male, Middle Aged, Time Factors, Vascular Resistance, Vasodilation, Sodium Chloride, Dietary

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