Correspondence

Salt-Sensitive Hypertension

N Engl J Med 2002; 347:448-449August 8, 2002

Article

To the Editor:

Johnson et al. (March 21 issue)1 address the mechanism of salt-sensitive hypertension but omit the most perplexing step: how sodium retention increases blood pressure. Figure 3 of their article shows an arrow from sodium retention to increased blood pressure but offers no hint as to how the former leads to the latter.

This step is perplexing because induced sodium retention (e.g., by intravenous infusion of saline or blood) does not immediately raise blood pressure; increased pressure occurs only if sodium retention is sustained, suggesting an indirect mechanism. Proposed mechanisms have included increased cardiac output, leading to a long-term, autoregulatory increase in total peripheral resistance, and increased blood volume, leading to the release of a ouabain-like substance, which increases total peripheral resistance. The mechanism of the increase in blood pressure in response to sodium retention is important because therapy might be directed at it.

Francis J. Haddy, M.D., Ph.D.
211 Second St. NW, No. 1607, Rochester, MN 55901-2896
tbhaddy@aol.com

1 References

1. 1

   Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B. Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med 2002;346:913-923
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The mechanisms by which sodium retention causes hypertension, while undoubtedly important, were outside the limits of our review, which focused on mechanisms by which subtle renal injury may lead to salt retention. Sustained sodium retention may induce hypertension by several mechanisms, some of which have been investigated extensively by Haddy and Pamnani.1 Sodium retention stimulates the production of Na⁺/K⁺ ATPase inhibitors (ouabain-like substances) that increase intracellular calcium concentrations, stimulate heart contractility and arteriolar vasoconstriction, and increase peripheral vascular resistance.2 In addition, sodium retention in susceptible persons may induce inappropriate central and sympathetic nervous system responses and increase the production of angiotensin II and catecholamines; this neurohormonal activation results in vascular remodeling, decreased arterial compliance, and oxidative stress.3 The free oxygen radicals thus generated may further promote impairment in vasodilator systems by reacting with nitric oxide and thereby decreasing local concentrations of nitric oxide.4

Richard J. Johnson, M.D.
Baylor College of Medicine, Houston, TX 77030
rjohnson@bcm.tmc.edu

Jaime Herrera-Acosta, M.D.
Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City 14080, Mexico

George F. Schreiner, M.D.
Scios, Sunnyvale, CA 94085

Bernardo Rodriguez-Iturbe, M.D.
Hospital Universitario, Maracaibo 4001-A, Venezuela

4 References

1. 1

   Haddy FJ, Pamnani MB. Role of dietary salt in hypertension. J Am Coll Nutr 1995;14:428-438
   Web of Science | Medline

2. 2

   Blaustein MP, Hamlyn JM. Pathogenesis of essential hypertension: a link between dietary salt and high blood pressure. Hypertension 1991;18:Suppl 3:184-195
   

3. 3

   Mancia G, Di Rienzo M, Parati G, Grassi G. Sympathetic activity, blood pressure variability and end organ damage in hypertension. J Hum Hypertens 1997;11:Suppl 1:S3-S8
   Web of Science | Medline

4. 4

   Wilcox CS. Reactive oxygen species: roles in blood pressure and kidney function. Curr Hypertens Rep 2002;4:160-166
   CrossRef | Web of Science | Medline