Impaired systolic and diastolic myocardial response to ET-1 and Ang II in heart failure.

• Type: Summary of Presentation in an International Conference
• Date: 2006

Authors

Brás-Silva C (Author) FMUP; Castro-Chaves P (Author) FMUP; Fontes-Sousa AP (Author) Other; Pimentel-Nunes P (Author) FMUP; Monteiro-Sousa D (Author) Other; Duarte AJ (Author) Other; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Journal of Heart Failure

Pages: 56-57

ESC Annual Congress 2006

Helsínquia, Finlândia, 17 a 20 de Junho de 2006

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Endothelin-1 (ET-1) and renin-angiotensin-aldosterone systems are two of the major neurohumoraJ systems activated in heart failure (HF). In the present study, we investigated, with a special emphasis on diastolic function, the myocardial effects of these two systems in normal and failing hearts, as well as, their interaction with the endocardiaJ endothelium (EE). New Zealand white rabbits were treated with Doxorubicin (lmg/kg, HF Group, n=28) or with saline (Control Group, n=40), administered intravenously twice weekly for 8 weeks into the marginal ear vein. The contractile effects of increasing doses of ET-1, Sara£otoxin $6c (SRTXc, selective agonlst of ETB receptors, non-specific ETB1/ETB2), IRL1620 (selective agonlst of endothelial ETB1 receptors), and Angiotensin II (Ang II) were studied in papillary muscles (n= 101, Krebs-Ringer: 1.SmM CaC12, 35°C) from the: (i) Control Group with intact EE; (ii) Control Group with damaged EE and (iii) HF Group. Only significant results (mean4-SEM, p<0.05) are given, expressed as % change from baseline. In the Control Group with intact EE, ET-1 and Ang II promoted a dosedependent positive inotropic effect. This effect was maintained in the absence of EE and in the HF Group in the case of ET-1, but was attenuated in these groups in response to Ang II. Both ET-1 and Ang II induced an increase in myocardial distensibility when in the presence of an intact EE. This effect was almost abolished after damaging the EE or in the HF Group. Selective stimulation of ETB receptors with SRTXc did not significantly alter myocardial function in muscles from the Control Group with intact EE, but induced a positive inotropic effect in the presence of a damaged EE or HE In contrast selective endothelial ETB1 receptor stimulation with IRL1620 induced a dose dependent negative inotropic effect in the Control Group with intact EE, effect that was abolished after damaging EE and reduced in the HF Group. This study showed that ET-1 and Ang II promote, in addition to the well known effects on systolic function, an increase in diastolic distensibility of the myocardium, that is depend on the EE functional integrity and that is almost absent in the failing myocardium. The response pattern to ETB receptors stimulation in the HF Group is suggestive of the presence of a dysfunctional EE. These results reinforce the importance of endotheliaJ ETB 1 receptors as markers of endothelial function and provide new elements for the comprehension of the pathophysiology of HF.

Language: English

Type (Professor's evaluation): Scientific

Notes: ESC Annual Congress 2006, published in journal, European Journal of Heart Failure. 2006; Vol.5(Suppl.1):56-57.