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 +/- 0.004 L/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 +/- 0.0020 L/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.