title: Hemodynamic effects of bosentan in patients with chronic heart failure.
abstract: A role of the potent and long-acting vasoconstrictor peptide endothelin-1 and the pathophysiology of chronic human heart failure has been postulated based upon indirect evidence such as elevated plasma endothelin-1 levels and their with the degree of hemodynamic impairment. The advent of specific of endothelin-1 receptor antagonists has provided the opportunity not only to directly evaluate its pathophysiological role but also to assess its potential role as a new approach to heart failure therapy. This brief review summarizes the evidence linking endothelin-1 to the pathophysiology of chronic heart failure and the clinical results obtained in patients during acute, intravenous and more prolonged, oral administration with bosentan, a mixed ET(A)/ET(B)-receptor antagonist. Bosentan acutely and during short-term oral therapy markedly improved hemodynamics in patients in addition to standard heart failure therapy, including an ACE-inhibitor. These effects were associated with a reduced responsiveness of the renin-angiotensin system to diuretic therapy and reduced basal plasma aldosterone levels. Although the hemodynamic and neurohumoral profile of short-term bosentan therapy looks promising for the treatment of patients with chronic heart failure appropriate trials will have to be performed to document clinical benefit during long-term therapy. Finally, the question remains open whether mixed endothelin-1 receptor antagonists like bosentan will have similar effects as compared to antagonists which block the ET(A) receptor only.
authors.affiliation: Division of Cardiology, University Hospital, Zürich, Switzerland. Wolfgang.Kiowski@dim.usz.ch
authors.forename: W
authors.initials: W
authors.lastname: Kiowski
authors.forename: G
authors.initials: G
authors.lastname: Sütsch
authors.forename: E
authors.initials: E
authors.lastname: Oechslin
authors.forename: O
authors.initials: O
authors.lastname: Bertel
mesh_terms: D000077300:Bosentan; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017466:Receptors, Endothelin / Q000502:physiology; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D017466:Receptors, Endothelin; D013449:Sulfonamides; D000077300:Bosentan