Cardiovascular endothelins: Essential regulators of cardiovascular homeostasis

• Type: Another Publication in an International Scientific Journal
• Date: 2006

Authors

Brunner, F (Author) Other; Bras Silva, C (Author) FCNAUP; Cerdeira, AS (Author) Other; Leite Moreira, AF (Author) FMUP

Journal

Title: PHARMACOLOGY & THERAPEUTICS

Vol. 111

Pages: 508-531

ISSN: 0163-7258

Publisher: Pergamon Press - Elsevier

Indexing

ISI Web of Knowledge - 144 Citations

Scopus - 169 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-JC5

DOI: 10.1016/j.pharmthera.2005.11.001

Abstract (EN): The endothelin (ET) system consists of 3 ET isopeptides, several isoforms of activating peptidases, and 2 G-protein-coupled receptors, ETA and ETB, that are linked to multiple signaling pathways. In the cardiovascular system, the components of the ET family are expressed in several tissues, notably the vascular endothelium, smooth muscle cells, and cardiomyocytes. There is general agreement that ETs play important physiological roles in the regulation of normal cardiovascular function, and excessive generation of ET isopeptides has been linked to major cardiovascular pathologies, including hypertension and heart failure. However, several recent clinical trials with ET receptor antagonists were disappointing. In the present review, the authors take the stance that ETs are mainly and foremost essential regulators of cardiovascular function, hence that antagonizing normal ET actions, even in patients, will potentially do more harm than good. To support this notion, we describe the predominant roles of ETs in blood vessels, which are (indirect) vasodilatation and ET clearance from plasma and interstitial spaces, against the background of the subcellular mechanisms mediating these effects. Furthermore, important roles of ETs in regulating and adapting heart functions to different needs are addressed, including recent progress in understanding the effects of ETs on diastolic function, adaptations to changes in preload, and the interactions between endocardial-derived ET-I and myocardial pump function. Finally, the potential dangers (and gains) resulting from the suppression of excessive generation or activity of ETs occurring in some cardiovascular pathological states, such as hypertension, myocardial ischemia, and heart failure, are discussed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 24