Effects of Physical and Pharmacological Interventions on Circulating Endothelin-1 Levels in Humans
Endothelin-1 (ET-1) is a 21 amino acid peptide produced by the endothelial cells that for its potent and long lasting vasoconstrictive action may be involved in a number of cardiovascular disorders [1, 2]. As to the mechanisms of regulation of ET-1, “in vitro” studies have shown that its secretion is controlled by numerous physical and humoral factors (Table 1); however “in vivo” studies addressed at investigating the physiological relevance of these factors may encounter difficulties for at least two reasons. One is that under normal conditions the concentration of ET-1 in blood is low (between 1–2 pg/ml); thus, since its secretion occurs by 80% or more towards the underlying vascular smooth muscle cells [3, 4], the changes in plasma ET-1 in response to stimuli may be too small to be detected with confidence with the present radioimmunoassays. The second reason is that there is no intracellular storage of ET-1 in most tissues [5, 6]; therefore, in order to observe modifications of the circulating peptide the duration of the stimulus must be long enough to activate “de novo” its synthesis. These reasons probably explain why most studies aimed at elevating plasma ET-1 have been inconclusive so far.
KeywordsAtrial Natriuretic Peptide Plasma Renin Activity Renovascular Hypertension Hypobaric Hypoxia Cold Pressor Test
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- 1.Haynes WG, Webb DJ (1993) The endothelin family of peptides: local hormones with diverse roles in health and disease? Clin Sci 84: 485–500Google Scholar
- 2.Löscher TF, Boulanger CM, Dohi Y, Yang Z (1992) Endothelium-derived contracting factors.Hypertension 19: 117–130Google Scholar
- 4.Wagner OF, Christ G, Woita J, Vierhapper H, Parzer S, Novotny PJ (1992) Polar secretion of endothelin-s by cultured endothelial cells. J Biol Chem 267:16 066–16 068Google Scholar
- 10.Morganti A, Giussani M, Sala C, Gazzano G, Marana I, Pierini A, Savoia MT, Ghio F, Cogo A, Zanchetti A. Effects of exposure to high altitude on plasma ET-1 in normal man. J Hypertens (in press)Google Scholar
- 11.Goerre S, Wenk M, Bartsch P, Löscher TF, Niroomand F, Hohenhaus E, Oelz O, Reinhart WH (1995) Endothelin-1 in pulmonary hypertension associated with high altitude exposure. Circulation 90 359–364Google Scholar
- 12.Chen SJ, Chen YF, Meng QC, Elton TS, Yano M, Oparil S (1994) Chronic blockade of endothelin-A receptors with BQ-123 prevents hypoxia induced pulmonary hypertension in the rat. Am J Hyper-tens 7 (2): 96A, abstract H32Google Scholar
- 15.Ferri C, Bellini C, De Angelis C, Perrone A, De Siati C, Di Francesco L, Properzi G, Santucci A, Bal-sano F (1994) Circulating endothelin-i levels in chronic hypoxemic patients. Am J Hypertens 7 (2): 135A, abstract L4Google Scholar
- 18.Morganti A, Giussani M, Ghio F, Pierini A, Savoia MT, Cogo A (1994) Endothelin releasing stimuli and calcium antagonist in normal and pathological conditions. J Hypertens 12 [Suppl 1]: S27 - S31Google Scholar
- 19.Hassi J, Rintamaki H, Ruskohao H, Leppaluoto J, Vuolteenaho 0 (1991) Plasma levels of endothelin-i and atrial natriuretic peptide in men during a 2-hour stay in a cold room. Acta Physiol Scand 142: 481–485Google Scholar
- 20.Koyama H, Tabatu T, Nishizawa Y, Inoue T, Morii H, Yamaji (1989) Plasma endothelin levels in patients with uremia. Lancet 333: 991–992Google Scholar
- 25.Giussani M, Cianci M, Gazzano G, Airoldi F, Turolo L, Ghio F, Martinoni A, Zanchetti A, Morganti A (1994) High levels of angiotensin II can increase endothelin-i production in patients with renovascular hypertension. Proceedings of the 15th meeting of the International Society of Hypertension. Melbourne 1994. J Hypertens 12 [Suppl 3]: S192Google Scholar