Correspondence

Preeclampsia — A State of Sympathetic Overactivity

N Engl J Med 1997; 336:1326-1327May 1, 1997

Article

To the Editor:

Schobel et al. (Nov. 14 issue)1 present convincing evidence, based on intraneural recordings of sympathetic-nerve activity in muscle-nerve fascicles, that preeclampsia is accompanied by sympathetic overactivity. We would like to offer an explanation for their findings that the authors did not consider. Recent evidence indicates that preeclampsia is an insulin-resistant state. Increased insulin levels and insulin resistance over and above those that already accompany pregnancy have been shown to predict pregnancy-associated hypertension.2 Notably, in pregnancy, as in the nonpregnant state, a relation between the insulin level and blood pressure persists despite the physiologic decrease in blood pressure.3 Hyperinsulinemia, in turn, has been shown to increase the sympathetic-nerve activity of skeletal muscle,4 the supposed site of the defect in glucose metabolism found in almost half of patients with essential hypertension.

In our own prospective study of pregnant women at risk for pregnancy-related hypertensive disorders (resistance index of the uteroplacental circulation, >0.58),5 the association between insulin resistance and preeclampsia was largely determined by the degree of obesity, a recognized risk factor for this condition.6 To enhance the interpretation of their findings, Schobel et al. should provide information on pregestational body weight and the body-mass index. It would be of interest to assess insulin sensitivity in their patients, since the defect in glucose metabolism has been shown to persist after delivery.

Reinold O.B. Gans, M.D., Ph.D.
Guus A. Dekker, M.D., Ph.D.
Free University Hospital, 1081 HV Amsterdam, the Netherlands

6 References

1. 1

   Schobel HP, Fischer T, Heuszer K, Geiger H, Schmieder RE. Preeclampsia -- a state of sympathetic overactivity. N Engl J Med 1996;335:1480-1485
   Full Text | Web of Science | Medline

2. 2

   Solomon CG, Graves SW, Greene MF, Seely EW. Glucose intolerance as a predictor of hypertension in pregnancy. Hypertension 1994;23:717-721
   Web of Science | Medline

3. 3

   Breschi MC, Seghieri G, Bartolomei G, Gironi A, Baldi S, Ferrannini E. Relation of birthweight to maternal plasma glucose and insulin concentrations during normal pregnancy. Diabetologia 1993;36:1315-1321
   CrossRef | Web of Science | Medline

4. 4

   Berne C, Fagius J, Pollare T, Hjemdahl P. The sympathetic response to euglycaemic hyperinsulinaemia: evidence from microelectrode nerve recordings in healthy subjects. Diabetologia 1992;35:873-879
   CrossRef | Web of Science | Medline

5. 5

   Gans ROB, Kraayenbrink AA, van Geijn HP, Dekker GA. Insulin resistance characterizes pregnant women that will develop preeclampsia. Am J Hypertens 1996;9:132A-132A abstract.
   CrossRef

6. 6

   Parazzini F, Bortolus R, Chatenoud L, et al. Risk factors for pregnancy-induced hypertension in women at high risk for the condition. Epidemiology 1996;7:306-308
   CrossRef | Web of Science | Medline

To the Editor:

Using microelectrodes to measure postganglionic action potentials in sympathetic fibers innervating blood vessels in skeletal muscle, Schobel et al. found that sympathetic activity in women with preeclampsia was more than three times as high as that in normotensive pregnant women. The authors discuss the conflicting results of previous catecholamine studies, but they do not mention that measurements of arterial plasma catecholamines seem to provide far better and more reliable data than measurements of urinary and venous plasma catecholamines, to which they refer.

We reported significantly increased arterial plasma catecholamine levels in patients with preeclampsia who were studied before the start of antihypertensive medication and under strictly standardized conditions.1-3 Strong correlations were observed between arterial plasma epinephrine levels and mean arterial blood pressure (r = 0.89), heart rate (r = 0.78), and platelet activation as estimated by β-thromboglobulin (r = 0.82). Our results provide specific information about important aspects of sympathetic and adrenal overactivity in preeclampsia.

Pål Øian, M.D.
Sverre E. Kjeldsen, M.D.
Ivar K. Eide, M.D.
Ullevål Hospital, N-0407 Oslo, Norway

3 References

1. 1

   Oian P, Kjeldsen SE, Eide I, Norman N. Increased plasma epinephrine correlates with blood pressure in preeclampsia. Clin Exp Hypertens 1984;3:61-73
   Web of Science

2. 2

   Oian P, Kjeldsen SE, Eide I, Maltau JM. Increased arterial catecholamines in pre-eclampsia. Acta Obstet Gynecol Scand 1986;65:613-617
   CrossRef | Web of Science | Medline

3. 3

   Oian P, Lande K, Kjeldsen SE, et al. Enhanced platelet release reaction related to arterial plasma adrenaline and blood pressure in pre-eclampsia. Br J Obstet Gynaecol 1986;93:548-553
   CrossRef | Medline

Author/Editor Response

The authors reply:

To the Editor: We certainly value the data provided by Øian et al., who found increased levels of arterial plasma catecholamines in patients with preeclampsia.1 Nevertheless, even if measurements of arterial plasma catecholamines seem to provide more reliable data than measurements of urinary or venous levels, the arterial values also merely represent the algebraic sum of different organ-specific increases or decreases in sympathetic activity that can occur with different reflexes and in different disease states. Since sympathetic nervous responses are patterned or regionalized, the global biochemical measures of venous, urinary, or arterial catecholamine levels constitute imperfect measures of sympathetic nervous function.

Gans and Dekker suggest that the increase in sympathetic-nerve activity that we found to be characteristic in women with preeclampsia may be explained by insulin resistance or obesity (a state characterized by hyperinsulinemia), or both. This is an interesting concept, but there are two problems with it. First, except for their own data,2 the study they cite3 does not offer convincing evidence that preeclampsia is an insulin-resistant state. This study found a significantly higher frequency of glucose intolerance among women in whom transient hypertension developed during pregnancy but not among women in whom preeclampsia developed. Second, although it is now well established that hyperinsulinemia stimulates sympathetic activity, the interaction among insulin resistance, sympathetic activation, and high blood pressure is still far from clear. Thus, most of the available data in the literature do not show any rise in blood pressure during experimentally induced hyperinsulinemia. Furthermore, the cited study by Parazzini et al.4 does not allow the conclusion that obesity is a “recognized risk factor” for preeclampsia, since this study also included patients with mild or moderate chronic hypertension and did not clearly define the group with preeclampsia.

In our study, the women with preeclampsia and the normotensive pregnant women were not obese and did not differ with regard to mean (±SE) pregestational body-mass index (23.6 ±1.2 and 23.9 ± 1.4, respectively). Unfortunately, we do not have any data on insulin sensitivity in our patients. Thus, whether insulin resistance or obesity or the combination accounts for the sympathetic overactivity and high blood pressure in women with preeclampsia remains an open question and requires further study.

Hans P. Schobel, M.D.
Roland E. Schmieder, M.D.
Thorsten Fischer, M.D.
University of Erlangen–Nürnberg, D-91054 Erlangen, Germany

4 References

1. 1

   Oian P, Kjeldsen SE, Eide I, Maltau JM. Increased arterial catecholamines in pre-eclampsia. Acta Obstet Gynecol Scand 1986;65:613-617
   CrossRef | Web of Science | Medline

2. 2

   Gans ROB, Kraayenbrink AA, van Geijn HP, Dekker GA. Insulin resistance characterizes pregnant women that will develop preeclampsia. Am J Hypertens 1996;9:132A-132A abstract.
   CrossRef

3. 3

   Solomon CG, Graves SW, Greene MF, Seely EW. Glucose intolerance as a predictor of hypertension in pregnancy. Hypertension 1994;23:717-721
   Web of Science | Medline

4. 4

   Parazzini F, Bortolus R, Chatenoud L, et al. Risk factors for pregnancy-induced hypertension in women at high risk for the condition. Epidemiology 1996;7:306-308
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Michael A. Belfort, George R. Saade, Charlotta Grunewald, Gary A. Dildy, Michael A. Varner, Henry Nisell. (1999) Effects of blood pressure on orbital and middle cerebral artery resistances in healthy pregnant women and women with preeclampsia. American Journal of Obstetrics and Gynecology 180:3, 601-607
   CrossRef

2. 2

   Gustaaf A. Dekker, Baha M. Sibai. (1999) The immunology of preeclampsia. Seminars in Perinatology 23:1, 24-33
   CrossRef