Negative inotropic effect of selective AT2 receptor stimulation and its modulation by endocardial endothelium, NO and prostaglandins.

• Type: Summary of Presentation in an International Conference
• Date: 2004

Authors

Leite-Moreira AF (Author) FMUP; Soares SS (Author) Other; Lima-Carneiro A (Author) Other; Castro-Chaves P (Author) FMUP

Conference proceedings International

Title: Journal of the American College of Cardiology

Pages: 492A-493A

54th Annual Scientific Session of the American-College-of-Cardiology

New Orleans, LA, 07 a 10 de março 2004

Indexing

ISI Web of Science

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Introduction: Angiotensin II (AT-II) 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-II, 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, which are not yet known. Methods: Effects of selective AT2 receptor activation were evaluated in rabbit right papillary muscles (n=35) by adding, to the superfusing solution (Krebs-Ringer; 1.8mM CaCl2; 35ºC), increasing doses of AT-II (10-8, 10-7, 10-6, 10-5 M) in the presence of a selective AT1 receptor antagonist (ZD7155, 10-6 M). Effects of selective AT2 receptor activation were evaluated in the absence (n=12) and in the presence of NG-nitro-L-Arginine (L-NA; 3*10-5 M; n=9) or Indomethacin (INDO; 10-3 M; n=7), as well as, in muscles without endocardial endothelium (EE; 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). Results: Selective AT2 stimulation induced a dose-dependent negative inotropic effect, decreasing, at 10-5 M of AT-II, 29.3±7.7% AT, 26.1±7.0% dT/dtmax, 27.9±7.5% dT/dtmin, 30.7±9.3% PS and 22.0±5.7% dL/dtmax. This effect was not influenced by L-NA (10-5 M of AT-II decreased 32.5±10.2% AT, 25.7±7.8% dT/dtmax, 26.7±8.6 dT/dtmin, 16.90±7.1 dL/dtmax) or INDO (10-5 M of AT-II decreased 34.4±7.1% AT, 27.9±6.1 dT/dtmax, 33.2±7.9 dT/dtmin, 20.2±5.0 dL/dtmax, 36.6±10.2 dL/dtmin, 25.3±7.1 PS), but was completely abolished after selective removal of the EE. Conclusions: Selective AT2 stimulation induces a negative inotropic effect, which is modulated by the EE, but not mediated by NO or prostaglandins. Such findings might help to better understand the therapeutic effects of selective AT1 antagonists, which are being increasingly used in for treating cardiovascular diseases

Language: English

Type (Professor's evaluation): Scientific

Notes: 54th Annual Scientific Session of the American-College-of-Cardiology, published in Journal, American College of Cardiology. 2004; 43(Suppl.A):492A-493A.