title: Endothelin receptors in the failing and nonfailing human heart.
abstract: BACKGROUND
  In patients with chronic heart failure (CHF), plasma endothelin-1 (ET-1) levels are increased. We studied whether the cardiac ET-receptor system is altered in CHF patients.
  
  
  RESULTS
  We assessed ET-evoked inositol phosphate (IP) formation in slices from right atria and left ventricles from 6 potential heart transplant donors (NFH) and 15 patients with end-stage CHF; in membranes from the same tissues, we studied ET-induced inhibition of isoprenaline- and forskolin-stimulated adenylyl cyclase and ET-receptor density. ET (10[-9] to 10[-6] mol/L, ET-1 >>> ET-3) increased IP formation in right atria and left ventricles through ET(A)-receptor stimulation in a concentration-dependent manner; no difference in potency or efficacy between NFH and CHF hearts was observed. ET-1 (10[-10] to 10[-6] mol/L), via ET(A)-receptor stimulation, inhibited isoprenaline- and forskolin-stimulated adenylyl cyclase in right atria but not in left ventricles, whereas carbachol inhibited adenylyl cyclase in both tissues; again, the potency and efficacy of ET- or carbachol-induced adenylyl cyclase inhibition was not different between NFH and CHF hearts. [125I]ET-1 binding revealed the coexistence of ET(A) and ET(B) receptors in both tissues; however, the density of ET(A) receptors was not significantly different between NFH and CHF hearts. Finally, the immunodetectable amount of left ventricular Gq/11 protein did not differ between NFH and CHF hearts.
  
  
  CONCLUSIONS
  In the human heart, ET(A) and ET(B) receptors coexist; however, only ET(A) receptors are of functional importance. In right atria, ET(A) receptors couple to IP formation and inhibition of adenylyl cyclase; in left ventricles, they couple only to IP formation. In end-stage CHF, the functional responsiveness of the cardiac ET(A)-receptor system is not altered.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Halle-Wittenberg, Halle, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Pönicke
authors.forename: M
authors.initials: M
authors.lastname: Vogelsang
authors.forename: M
authors.initials: M
authors.lastname: Heinroth
authors.forename: K
authors.initials: K
authors.lastname: Becker
authors.forename: O
authors.initials: O
authors.lastname: Zolk
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: H R
authors.initials: HR
authors.lastname: Zerkowski
authors.forename: O E
authors.initials: OE
authors.lastname: Brodde
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000737:chemistry; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D017466:Receptors, Endothelin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases