ENDOTHELIN-1 AND THE REGULATION OF VASCULAR TONE

被引:59
作者
LA, M
REID, JJ
机构
[1] Pharmacology Research Unit, Department of Medical Laboratory Science, Royal Melbourne Institute of Technology, Melbourne, Victoria
关键词
ENDOTHELIN-1; ENDOTHELIN CONVERTING ENZYME (ECE); ENDOTHELIN RECEPTOR ANTAGONISTS; ENDOTHELIUM; ET(A) RECEPTORS; ET(B) RECEPTORS; VASOCONSTRICTION; VASODILATATION;
D O I
10.1111/j.1440-1681.1995.tb02008.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. In 1988, Yanagisawa et al. reported the presence of a potent peptide from the supernatant of porcine endothelial cells. This was later named endothelin-1 (ET-1) and was found to belong to a new family of vasoconstrictor peptides. There are at least three isoforms of endothelin: ET-1, endothelin-2 and endothelin-3. 2. ET-1 is produced from a larger precursor molecule by endothelin converting enzyme (ECE); there may be a number of ECE but the most physiologically relevant appears to be a membrane-bound neutral metalloprotease. The endothelin precursor is produced on demand and is regulated at the mRNA level. 3. Two subtypes of mammalian endothelin receptors have been cloned and sequenced: ET(A) receptors which mediate vasoconstriction and ET(B) receptors which mediate both vasoconstriction and vasodilatation. However, functional studies have indicated that other subtypes of endothelin receptors may exist. 4. ET-1 has a wide range of biological actions apart from its direct effects on vascular tone, including constriction of nonvascular smooth muscle, cardiac effects, mitogenesis and stimulation of the release of hormones such as atrial natriuretic peptide and prostacyclin. At low concentrations which have no direct vasoconstrictor action, ET-1 potentiates the effect of other vasoconstrictor agonists. 5. The precise role of ET-1 in health and disease is not well defined at present; however, there are indications that it may have a role in the pathogenesis of some cardiovascular disease states, including subarachnoid haemorrhage, renal ischaemia and certain types of hypertension.
引用
收藏
页码:315 / 323
页数:9
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