Angiotensin II-induced increase in myocardial distensibility and its modulation by the endocardial endothelium in the rabbit heart

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Castro-Chaves P (Author) FMUP; Fontes-Carvalho R (Author) FMUP; Pintalhão M (Author) FMUP; Pedro Pimentel-Nunes (Author) FMUP; Leite-Moreira AF (Author) FMUP

Journal

Title: Experimental Physiology

Vol. 94 No. 3

Pages: 665-674

ISSN: 0958-0670

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-003-JGD

DOI: 10.1113/expphysiol.2008.046458

Abstract (EN): As recently demonstrated, angiotensin II (Ang II) induces an increase in myocardial distensibility. Although endothelin-1 and the endocardial endothelium (EE) also modulate myocardial diastolic properties, their interaction with Ang II at this level has not yet been investigated. Increasing concentrations of Ang II (from 10(-8) to 10(-5) m) were studied in rabbit right papillary muscles in the following conditions: (1) baseline; (2) after selective removal of EE with Triton X-100; and (3) with intact EE in presence of a non-selective endothelin receptor antagonist (PD-145065), a selective endothelin type A receptor antagonist (BQ-123), an inhibitor of nitric oxide synthesis (N(G)-nitro-l-arginine (l-NA) or an inhibitor of the NAD(P)H oxidase (apocynin). At baseline, Ang II induced a concentration-dependent positive inotropic effect and an increase in passive muscle length (L) up to 1.020 +/- 0.004L/L(max). After restoring muscle length to maximal physiological length (L(max)), passive tension decreased by 46.1 +/- 4.0%. When the EE was removed, the effect on myocardial distensibility was abolished. With intact EE in presence of PD-145065, BQ-123 or l-NA, the effects of Ang II on myocardial distensibility were attenuated, with a maximal increase in passive muscle length of 1.0087 +/- 0.0012, 1.0068 +/- 0.0022 and 1.0066 +/- 0.0020L/L(max) and a decrease in resting tension of 22.6 +/- 3.6, 16.1 +/- 6.0 and 20.4 +/- 5.6%, respectively. In the presence of apocynin, the effect on myocardial distensibility was abolished. In conclusion, the Ang II-dependent acute increase in myocardial distensibility is abolished by the selective removal of the EE and attenuated in the presence of endothelin-1 receptor antagonists, an inhibitor of nitric oxide synthesis or an inhibitor of NAD(P)H oxidase.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10