BACKGROUND: Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin(A) (ETA) receptor antagonist, on both heart and myocardial contractility in rats with CHF. METHODS AND RESULTS: We used the left coronary artery-ligated rat model of CHF (CHF rats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHF rats than in the sham-operated rats (P<.01). In the left ventricle, the expression prepro-ET-1 mRNA was markedly higher in the CHF rats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHF rats than in the sham-operated rats (500+/-41 versus 102+/-10 pg/g tissue, P<.01). Myocardial ET receptors were significantly higher in the CHF rats than in the sham-operated rats (243+/-20 versus 155+/-17 fmol/mg protein, P<.05). In the CHF rats, intravenous BQ-123 infusion (0.1 mg x kg(-1) x min(-1) for 120 minutes) significantly decreased both heart rate (P<.01) and LV+dP x dt(max) (P<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats. CONCLUSIONS: In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHF rats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt(max) in the CHF rats but not in the sham-operated rats. Therefore, the ET receptor-mediated signal transduction system in the heart appears to be markedly stimulated in the CHF rats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.
BACKGROUND: Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin(A) (ETA) receptor antagonist, on both heart and myocardial contractility in rats with CHF. METHODS AND RESULTS: We used the left coronary artery-ligated rat model of CHF (CHFrats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHFrats than in the sham-operated rats (P<.01). In the left ventricle, the expression prepro-ET-1 mRNA was markedly higher in the CHFrats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHFrats than in the sham-operated rats (500+/-41 versus 102+/-10 pg/g tissue, P<.01). Myocardial ET receptors were significantly higher in the CHFrats than in the sham-operated rats (243+/-20 versus 155+/-17 fmol/mg protein, P<.05). In the CHFrats, intravenous BQ-123 infusion (0.1 mg x kg(-1) x min(-1) for 120 minutes) significantly decreased both heart rate (P<.01) and LV+dP x dt(max) (P<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats. CONCLUSIONS: In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHFrats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt(max) in the CHFrats but not in the sham-operated rats. Therefore, the ET receptor-mediated signal transduction system in the heart appears to be markedly stimulated in the CHFrats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.
Authors: Amy C Y Lo; Maggie K L Fung; C L Au; Theobald S K Chan; Brian Sauer; Stephen S M Chung; Sookja K Chung Journal: Transgenic Res Date: 2004-04 Impact factor: 2.788
Authors: Y Reisner; G Meiry; N Zeevi-Levin; D Y Barac; I Reiter; Z Abassi; N Ziv; S Kostin; J Schaper; M R Rosen; O Binah Journal: J Cell Mol Med Date: 2009-03 Impact factor: 5.310