NO and prostaglandins are required for the increase in myocardial distensibility induced by ET-1.

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

Authors

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

Conference proceedings International

Title: European Journal of Heart Failure

Initial page: 74

ESC Annual Congress 2006

Helsínquia, Finlândia, 17 a 20 de Junho de 2006

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

CORDIS: Health sciences > Medical sciences > Medicine > Cardiology

Other information

Resumo (PT): Endothelin-1 (ET-1) increases myocardial distensibility in conditions of cardiac overload, an effect that was shown to be mediated by ETA receptors and modulated by the endocardiaJ endothelium (EE). The present study investigated the role of NO and prostaglandins on ET-1 induced diastolic distensibility. The effects of ET-1 (0.1, 1, 10 nM) were tested in papillary muscles isolated from New Zealand white rabbits (Krebs-Ringer; 1.8mM CaC12, 35°C) in the presence of: (i) intact endocardial endothelium (EE) (n=9); (ii) damaged EE (0.5% Triton X-100, n=10); (iii) NGNitro-L-Arginlne (LNA; nitric oxide synthase inhibitor, n=9), and (iv) Indomethacin (INDO; cyclooxigenase inhibitor, n=6). Reported parameters include: active tension (AT), ma, ximum velocities of tension rise (dT/dtma, x) and tension decline (dT/dtmin), resting tension at the beginnlng (RTbeg) and at the end (RTend) of the isometric twitch. Only significant results (mean4-SEM, p<0.05) are given, expressed as % change from baseline. In papillary muscles with intact EE, ET-1 induced dose dependent positive inotropic and lusitropic effects: AT increased 15.34-5.4%, 47.24-9.8% and 88.64-18.3%; dT/dtma,x increased 15.44-5.9%, 47.14-12.3% and 103.74-21.5%; and dT/dtmin increased 13.34-4.9%, 42.44-6.8% and 85.64-16.9%. These effects were maintained when ET-1 was given after damaging EE (AT increased 15.14-4.5%, 47.74-10.3% and 74.14-12.5%; dT/dtma,x increased 11.54-3.6%, 48.84-8.7% and 97.74-13.5%; and dT/dtmin increased 8.04-2.7%, 38.44-14.0% and 60.04-14.4%), in the presence of LNA (AT increased 8.44-2.4%, 31.24-7.7% and 84.34-19.3%, dT/dtma,x increased 14.24-4.1%; 45.44-7.5% and 126.74-16.6%, and dT/dtmin increased 4.94-2.4%, 32.24-9.4% and 69.84-24.8%) orin the presence of INDO (AT increased 8.04-2.3%, 34.44-14.2% and 87.64-33.0%, dT/dtmax increased 5.74-2.4%; 32.74-14.4% and 109.64-40.0%, and dT/dtmin increased 6.54-2.4%, 29.44-17.0% and 87.74-40.0%). ET-1 reduced RTend (increased diastolic distensibility) by 3.24-1.3%, 6.04-1.6% and 8.84-2.7% (at 0.1, 1 and 10 nM, respectively), in muscles with intact EE, effect that was completely abolished after damaging EE or in the presence of LNA or INDO. This study demonstrated that the increase in myocardial distensibility induced by ET-1 is dependent of nitric oxide and prostaglandin release. As this increase in diastolic distensibilty might contribute to ventricular dilation, these findings might improve our understanding about the role of ET-1 and endothelial dysfunction in the pathophysiology of heart failure.

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):74-74.