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ENDOTHELIN‐1 AS A MEDIATOR IN CARDIOVASCULAR DISEASE
Author(s) -
Kelly John J,
Whitworth Judith A
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03011.x
Subject(s) - mediator , endothelin receptor , medicine , endothelin 1 , disease , cardiology , endocrinology , receptor
1. Brachial artery infusion of endothelin (ET)‐1 causes transient vasodilatation followed by sustained vasoconstriction of the forearm vascular bed, whereas ET‐1 antagonists cause sustained vasodilatation. These data suggest that ET‐1 contributes to basal vascular tone. 2. Systemic infusion of ET‐1 increases blood pressure and total peripheral vascular resistance and reduces heart rate and cardiac output. The renal and pulmonary circulations are particularly sensitive to the vasoconstrictor effects of ET‐1. Systemic infusion of the ET A/B receptor antagonist TAK‐044 reduces mean arterial pressure and peripheral vascular resistance. 3. Plasma ET‐1 concentrations are not elevated in essential hypertension; however, insulin resistance may be a major determinant of plasma ET‐1 concentrations. Vascular sensitivity to ET‐1 is normal or may be increased in essential hypertension. 4. Plasma ET‐1 concentrations are increased in moderate and severe heart failure and are correlated with clinical and haemodynamic measures of severity. Endothelin‐1 contributes to increased vascular tone in cardiac failure. 5. Plasma ET‐1 concentrations increase following myocardial infarction and persistent elevation predicts an increased mortality within the subsequent 12 months. 6. Preliminary data suggest that interventions that reduce the activity of the endothelin system may have a beneficial effect in heart failure and myocardial infarction.