Regulation of left ventricular relaxation in the isolated guinea-pig heart by endogenous endothelin
Open Access
- 1 January 1997
- journal article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 33 (1) , 131-138
- https://doi.org/10.1016/s0008-6363(96)00174-5
Abstract
Objective: To examine the effects of endogenous endothelin-1 on cardiac contraction in the isolated heart using endothelin receptor antagonists. Methods: Isolated ejecting guinea-pig hearts were perfused with Krebs buffer (1 μM indomethacin) at 37°C, constant loading and heart rate, and high-fidelity left ventricular pressure was monitored by an apical 2F Millar catheter. The effects of the following interventions on left ventricular performance and coronary flow were determined: (a) no treatment (i.e., time controls) (n = 8); (b) the specific ETA receptor antagonist, BQ123 (1 μM, n = 8); (c) the specific ETB receptor antagonist, IRL1038 (0.1 μM, n = 4; 1 μM, n = 6); (d) exogenous endothelin-1 (0.01 nM, n = 6; 0.1 nM, n = 6); (e) the specific ETB receptor agonist, BQ3020 (5 nM, n = 8). Results: All parameters were stable in control (untreated) hearts. BQ123 induced progressive acceleration of early left ventricular pressure decline and a fall in left ventricular end-diastolic pressure with no effect on peak left ventricular pressure, dP/dtmax, stroke volume or coronary flow. IRL1038 had no effect on any of these parameters. In contrast, exogenous endothelin-1 exerted potent vasoconstrictor effects associated with a fall in peak left ventricular pressure, dP/dtmax and stroke volume. Similar changes were observed with BQ3020. Concentrations of endothelin-1 < 0.1 nM, which had no vasoconstrictor effect, produced no change in LV function. Conclusions: These data indicate that basal intracardiac release of endothelin-1 significantly delays LV relaxation in the isolated guinea-pig heart, but has no effect on coronary flow. The contrasting effects of endogenous endothelin-1 (elicited by BQ123) and exogenous endothelin-1 are likely to reflect differences in their site of action and in their effective concentrations at these sites.Keywords
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