Negative inotropic effect of selective AT2 receptor stimulation and its underlying mechanisms.

• Type: Summary of Presentation in an International Conference
• Date: 2005

Authors

Soares S (Author) Other; Castro-Chaves P (Author) FMUP; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Journal of Heart Failure

Initial page: 123

ESC Annual Congress 2005

Stockholm, Sweden , 03 a 07 de Setembro de 2005

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Angiotensin II (AT-H) is an endogenous peptide whose effects are mediated by two types of receptors, AT1 and AT2. AT1 receptors are responsible for the vasoconstrictor, positive inotropic and growth promoting properties of AT-H, while AT2 receptors have been linked to vasodilator and anti-mitogenic properties. In this study we investigated the effects of selective AT2 receptor stimulation on myocardial contractility. Effects of selective AT2 receptor activation were evaluated in rabbit fight papillary muscles (n=51) by adding, to the superfusing solution (Krebs- Ringer; 1.8mM CaC12; 35°C), increasing doses of AT-II (10e-8, 10e-7, 10e-6, 10e-5 M) in the presence of a selective AT1 receptor antagonist (ZD7155, 10e-6 M). Selective AT2 receptor activation was performed in the absence (n=12) and in the presence of NG-nitro-L-Arginine (L-NA; 3"10e-5 M; n=9), Indomethacin (INDO; 10e-5 M; n=7) or Proadifen (PRO; 10e-6M; n=9), as well as, after removal of endocardial endothelium (EE; n=7). Finally, the effect of AT-2 receptor stimulation was studied in the presence of a nonselective antagonist of endothelin- 1 (ET- 1 ) receptors in intact endothelium muscle preparations (PD-145065; 10e-6M; n=7). Calculated parameters: active tension (AT), peak rates of tension rise and decline (dT/dtmax and dT/dtmin, respectively), peak shortening (PS) and peak rate of shortening (dL/dtmax). Results are presented as mean+SEM in % of baseline (p<0.05). Selective AT2 stimulation induced a dose-dependent negative inotropic effect, decreasing, at 10e-5 M of AT-II, 29.34-7.7% AT, 26.14-7.0% dT/dtmax, 27.9-t-7.5% dT/dtmin, 30.7-t-9.3% PS and 22.0-t-5.7% dL/dtmax. This effect was not influenced by L-NA (-32.54-10.2% AT, -25.7-t-7.8% dT/dtmax, -26.7-t-8.6 dT/dtmin, -16.90-t-7.1 dL/dtmax), INDO (-34.4-t-7.1% AT, -27.9-t-6.1 dT/dtmax, -33.2-t-7.9 dT/dtmin, - 20.2-t-5.0 dL/dtmax, -36.6-t-10.2 dL/dtmin, -25.3-t-7,1 PS) or PRO (-26.0-t-8.3% AT, -25.5-t-6.6% dT/dtmax, -26.4-t-7.6% dT/dtmin, - 23.7-t-8.0% PS, -22.9-t-7.0% dL/dtmax, -30.4-t-9.7% dL/dtmin), but was completely abolished after selective removal of the EE. In the presence of PD-145065, the effect was attenuated (-12.34-5.4% TA, -11.94-4.6 dT/dtmax, -7.5-t-6.5 dT/dtmin, -12.7+4.2%EM, -12.0-t-3.1% dL/dtmax e -11.24-7.3 dL/dtmin. Selective AT2 stimulation induces a negative inotropic effect, which is modulated by the EE, but mediated neither by NO, prostaglandins nor EDIIF. The effect is partially attenuated by the inhibition of ET-1 receptors. Such findings might help to better understand the therapeutic effects of selective AT 1 antagonists.

Language: English

Type (Professor's evaluation): Scientific

Notes: ESC Annual Congress 2005, published in journal, European Journal of Heart Failure. 2005; Vol.4(Suppl.1):123-123.