Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension.

Annals of the Rheumatic Diseases - Tập 54 Số 9 - Trang 730-734 - 1995
Sergio Morelli1, Claudio Ferri2, L. Di Francesco2, R Baldoncini2, Marta Carlesimo3, Ugo Bottoni3, G. Properzi4, Annalisa Santucci4
1University of Rome La Sapienza, Institute of I Clinica Medica, Andrea Cesalpino Foundation, Rome, Italy.
2University of Rome, La Sapienza
3Institute of Dermatology
4University of L'Aquila

Tóm tắt

OBJECTIVES--To investigate the behaviour of circulating endothelin-1 (ET-1) in patients affected by systemic sclerosis and to elucidate the relationship between systemic and pulmonary plasma peptide and arterial pressure levels. METHODS--Plasma ET-1 concentrations were determined in 48 patients affected by systemic sclerosis (41 women, seven men; mean age 47.2 (SD 5.5) years) with or without systemic or pulmonary hypertension (or both). A group of 18 normal volunteers served as controls (15 women, three men; mean age 45.0 (10.1) years). RESULTS--Plasma ET-1 levels were significantly greater in patients affected by systemic sclerosis (1.65 (0.29) pg/ml) than in controls (0.63 (0.19) pg/ml) (p < 0.0001). Pulmonary artery systolic hypertension alone was present in 14 patients with systemic sclerosis (50.5 (8.49) mm Hg, range 37-67 mm Hg), and systemic hypertension alone (160.7 (5.9)/100.6 (3.2) mm Hg) was present in 11 patients. Both conditions were present in 12 patients, while 11 patients had systemic hypertension. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension alone (1.62 (0.21) pg/ml) and those with systemic hypertension alone (1.65 (0.43) pg/ml). In particular, patients with normal pulmonary artery and systemic pressures (n = 11) had plasma ET-1 concentrations identical to those found in patients (n = 12) with both pulmonary and systemic hypertension (1.70 (0.15) v 1.64 (0.35) pg/ml, respectively). No correlations were observed between plasma ET-1 and either pulmonary or systemic pressures. CONCLUSION--Systemic sclerosis is characterised by increased plasma ET-1 levels, but neither pulmonary nor systemic hypertension are accompanied by further increase in plasma peptide levels.

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Tài liệu tham khảo

Greenwald G I, Tashkin D P, Gong H Jr, et al. Longitudinal changes in lung function and respiratory symptoms in progressive systemic sclerosis. Am _7 Med 1987; 83: 83-92.

Lee P, Langevitz P, Buskila D. Mortality in systemic sclerosis (scleroderma). Arthritis Rheum 1990; 33: S156.

Gilliland B C. Progressive systemic sclerosis (diffuse scleroderma). In: Braunwald E, Isselbaker K J, Petersdorf Haison 's R G, Wilson principles of JinDt,erMnaarltimnedJicBi,neF.aucNieAwS,Yoerdks:. McGraw-HillInc, 1987; 1828-32.

Kahaleh M B. Endothelin, an endothelial-dependent vasoconstrictor in scleroderma. Arthnrtis Rheum 1991; 34: 978-83.

Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980; 23: 581-90.

Wagner 0 F, Nowotny P, Vierhapper H. Plasma concentrations of endothelin in man: artero-venous differences and release during venous stasis. Eur_7 Clin Invest 1990; 20: 502-5.

Hatle L, Brubakk A, Tromsdal A, Angelsen B. Non invasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. BrHeartj_ 1978; 40: 131-40.

Currie P J, Seward J B, Chan K L, et al. Continuous-wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. JAm CollCardiol 1985; 6: 6750-6.

LeRoy E C, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. _Rheumatol 1988; 15: 202-5.

Yamane K, Kashiwagi H, Suzuki N, et al. Elevated plasma levels of endothelin-I in systemic sclerosis. Arthritis Rheuni 1991; 34: 243-4.

Cody R J, Haas CG J, Binklev P F, Capers Q, Kellev R. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. Circulation 1992; 85: 504-9.

Stewart D J, Levy R D, Cemacek P, Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Int Med 1991; 114: 454-9.

McMurray J J, Ray S G, Abdullah I, Dargie H J, Morton J J. Plasma endothelin in chronic heart failure. Circulationz 1992; 85: 1374-9.

Margulies K B, Hildebrand F L, Lerman A, Perella M A, Burnett J C. Increased endothelin in experimental heart failure. Circulation 1990; 82: 2226-30.

Saito Y, Nakao K, Mukoyama M, Imura H. Increased plasma endothelin level in patient with essential hvpertension [letter]. NEngJ7Med 1990; 322: 205.

Shichiri M, Hirata Y, Ando K, et al. Plasma endothelin-1 levels in hypertension and chronic renal failure. Hxpertension 1990; 15: 493-6.

Summer D. Lies, damned lies-or statistics? _7 Hjpertens 1992; 10: 3-8.

Vancheeswaran R, Magoulas T, Efrat G, et al. Circulating endothelin-l levels in systemic sclerosis subsets. A marker of fibrosis or vascular dysfunction? 7 Rheumatol 1994; 21: 1838-44.

Yoshimoto S, Ishizaki Y, Mori A, et al. The role of cerebral microvessel endothelium in regulation of cerebral blood flow through production of endothelin-1. ] Vasc Med Biol 1990; 2: 178.

De Nucci G, Thomas R, D'Orleans-Juste P, et al. Pressor effects of endothelin are limited by its removal in the pulmonary circulation and by release of prostacyclin and endothelium derived relaxing factor. Proc Natl Acad Sci USA 1988; 85: 9797-800.

Rubanyi G M, Parker Botelho L H. Endothelins. FASEB 7 1991; 5: 2713-20.

Yanagisawa M, Kurihara H, Kimura S, Tamake Y, Kobayashi M, Mitsui Y. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411-5.

Schuller M, Stetter R, Skrabal S, Missbichler A, Woloszezuk W, Hartter E. Radioimmunoassay of immunoreactive C-terminal big-endothelin(22-38). Cln Chemt Clin Biochem 1991; 29: 147-50. Eury

Pacher R, Berger-Klein J, Globits S, et al. Plasma bigendothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. Amii Y Cardiol 1993; 71: 1293-9.

Yokokawa K, Takahara M, Kohno K, et al. Hypertension associated with endothelin-secreting malignant hemangioendothelioma. Am Intern Med 1991; 114: 213-5.

Schiffrin E L, Thibault G. Plasma endothelin in human essential hypertension. Am YHypertens 1991; 4: 303-8.

Davenport A P, Ashby M J, Easton P, et al. A sensitive radioimmunoassav measuring endothelin-like immunoreactivits in human plasma. Comparison of levels in patients with essential hypertension and normotensive control subjects. Clin Sci 1990; 78: 261-4.

Luscher T F, Seo B, Buhler F R. Potential role of endothelin in hypertension. Controversy on endothelin in hypertension.Hypertension 1993; 21: 752-7.