Summary
The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients given Pl completed the entire experimental protocol, including monthly visits for metabolic and hormonal measurements, as well as a bicycle exercise test with arterial catheterisation for haemodynamic and catecholamine measurements performed before and after 3 months of treatment.
A progressive significant decrease in body weight, averaging 6.0 kg after 3 months was observed in the dF-treated group, whereas loss of weight in the placebo group (1.4 kg) was not significant. While blood pressure and noradrenergic activity, assessed as changes in the plasma levels and urinary excretion of norepinephrine, remained unaffected in the Pl group, a significant drop in the supine systolic and diastolic blood pressures, as well as in the resting venous norepinephrine level and in urinary norepinephrine excretion was found after the first month of dF administration. In addition, the exercise-induced rise in systolic and diastolic blood pressure, as well as in arterial plasma norepinephrine and epinephrine concentrations, was significantly reduced after 3 months of dF administration; there were no such changes in the Pl-treated group.
The results of the present study indicate that, in addition to the weight-reducing effect of dexfenfluramine, its hypotensive effect may be mediated by a decrease in noradrenergic activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Van Itallie TB (1985) Health implications of overweight and obesity in the United States. Ann Intern Med 103: 983–988
Dustan HP (1985) Obesity and hypertension. Ann Intern Med 103: 1047–1049
Staessen J, Fagard R, Lijnen P, Amery A (1989) Body weight, sodium intake and blood pressure. J Hypertens 7 [Suppl 1]: 519–523
Krieger DR, Landsberg L (1988) Mechanisms in obesity-related hypertension: role of insulin and catecholamines. Am J Hypertens 1: 84–90
Jung RT, Shetty PS, Barrand M, Callingham BA, James WPT (1979) Role of catecholamines in hypotensive response to dieting. Br Med J 1: 12–13
James W, Harraldsdottir J, Liddel F, Jung RT, Shetty PS (1981) Autonomic responsiveness in obesity with and without hypertension. Int J Obesity 5 [Suppl 1]: 73–78
Sowers JR, Whitfield LA, Catania RA, Stern F, Tuck ML, Dornfeld L, Maxwell M (1982) Role of the sympathetic nervous system in blood pressure maintenance in obesity. J Clin Endocrinol Metab 54: 1181–1186
Kolanowski J (1985) Modifications du bilan de sodium et de la tension arterielle au cours de la diète protidique chez les sujets obèses. Cah Nutr Diet 20: 47–50
Reisin E, Abel R, Modan M, Silverberg DS, Eliahov HE, Modan B (1978) Effect of weight loss without salt restriction on the reduction of blood pressure in overweight hypertensive patients. N Engl J Med 298: 1–6
Berchtold P, Jörgens U, Kemmer FW, Berger M (1982) Obesity and hypertension: Cardiovascular response to weight reduction. Hypertension 4 [Suppl III]: 50–55
Guy-Grand B, Apfelbaum M, Crepaldi G, Gries A, Lefebvre P, Turner P (1989) International trial of long-term dexfenfluramine in obesity. Lancet II: 1142–1145
Garattini S (1987) Mechanisms of the anorectic activity of dextrofenfluramine. In: Bender AE and Brookes LJ (ed) Body weight control. Churchill Livingstone, pp 261–270
Waal-Manning HJ, Simpson FO (1969) Fenfluramine in obese patients on various antihypertensive drugs, double-blind and controlled trial. Lancet II: 1392–1395
Lake CR, Coleman MD, Ziegler MG, Murphy DL (1979) Fenfluramine and its effect on the sympathetic nervous system in man. Curr Med Res Opin 6 [Suppl 1]: 63–72
Detry JM, Melin J, Brasseur LA, Rousseau MF (1981) Haemodynamic effects of Malsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exortional angina pectoris. Am J Cardiol 47: 109–115
Eriksson BM, Persson BA (1982) Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection. J Chromatogr 228: 143–154
Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New York
Daniel WW (1978) Applied nonparametric statistics. Houghton Mifflin, Boston
Enzi G, Crepaldi G, Inelmen EM, Bruni R, Baggio B (1988) Efficacy and safety of dexfenfluramine in obese patients: a multicenter study. Clin Neuropharmacol 11 [Suppl 1]: S173-S178
Finer N, Craddock D, Lavielle R, Keen H (1988) Effect of 6-month therapy with dexfenfluramine in obese patients: studies in the United Kingdom. Clin Neuropharmacol 11 [Suppl 1]: S179-S186
Andersson B, Zimmermann ME, Hedner T, Björntorp P (1991) Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women. Eur J Clin Pharmacol 40: 249–254
Hudson KD (1977) The anorectic and hypotensive effect of fenfluramine in obesity. JR Coll Gen Pract 27: 497
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kolanowski, J., Younis, L.T., Vanbutsele, R. et al. Effect of dexfenfluramine treatment on body weight, blood pressure and noradrenergic activity in obese hypertensive patients. Eur J Clin Pharmacol 42, 599–605 (1992). https://doi.org/10.1007/BF00265922
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00265922