title: Cardiac endothelin and big endothelin in right-heart hypertrophy due to monocrotaline-induced pulmonary hypertension in rat.
abstract: OBJECTIVE
  Recent observations suggest the existence of a myocardial endothelin (ET) system and its possible involvement in left-ventricular myocardial hypertrophy and failure. However, nothing is known about the role of myocardial ET in right-ventricular hypertrophy.
  
  
  METHODS
  Rats (80-100 g) were given an intraperitoneal injection of saline (controls) or monocrotaline (50 mg/kg) resulting in pulmonary hypertension-induced myocardial hypertrophy (n = 11 in both groups). After 10 weeks, the animals were sacrificed and hearts perfused in vitro to determine levels of big ET-1 and ET-1 in coronary effluent, interstitial fluid and ventricular tissue homogenates; plasma levels were also determined.
  
  
  RESULTS
  In monocrotaline-treated animals, weights of right ventricles were 1.5 and of right atria 1.8-fold higher than in controls (p < 0.05), indicating substantial right-ventricular hypertrophy as also evident from greatly increased myocardial production of atrial natriuretic peptide. Left-ventricular weights were not different. Release of big ET-1 in coronary effluent, and of ET-1 in coronary effluent and interstitial transudate were similar in control and hypertrophic hearts (p > 0.05). Disruption of endothelium with collagenase reduced release of both peptides close to zero, indicating endothelial (not myocardial) origin of the peptides. Levels of big ET-1 and ET-1 were similar in left ventricles of both experimental groups, but lower in right ventricles of hypertrophic than control hearts (p < 0.05), reflecting increased tissue mass rather than reduced peptide production. On the other hand, plasma levels of both peptides and of ANP were twofold and levels of angiotensin II 1.3-fold higher in rats with right-heart hypertrophy than in controls (p < 0.05 in each case).
  
  
  CONCLUSIONS
  These data do not support a role for local cardiac ET-1 and/or big ET-1 in right-ventricular hypertrophy, but point to blood-borne endothelins as possible mediators.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria. friedrich.brunner@kfunigraz.ac.at
authors.forename: F
authors.initials: F
authors.lastname: Brunner
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism*; D016232:Endothelins / Q000032:analysis / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000378:metabolism; D017380:Hypertrophy, Right Ventricular / Q000209:etiology* / Q000378:metabolism; D016686:Monocrotaline; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D011042:Poisons; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011042:Poisons; D011498:Protein Precursors; D000804:Angiotensin II; D016686:Monocrotaline; D009320:Atrial Natriuretic Factor