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Endothelin‐1 receptor antagonism does not influence myocardial function in hypertensive dogs
Author(s) -
Pascale Massart,
D Hodeige,
Henri Van Mechelen,
Guy R. Heyndrickx,
Julian Donckier
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00374.x
Subject(s) - bosentan , medicine , endothelin receptor , endothelin receptor antagonist , cardiology , contractility , blood pressure , vasoconstriction , inotrope , ventricular pressure , anesthesia , heart rate , vascular resistance , receptor
Background As endothelin‐1 exerts positive inotropic effects, the present study evaluated whether the hypotensive effects of the endothelin‐1 receptor antagonist bosentan were partially related to a decrease in myocardial performance. Methods In group I, eight anaesthetized open‐chest dogs with perinephritic hypertension received four cumulative doses of bosentan (B1–B4). In group II, eight animals received the same doses of bosentan after autonomic blockade. Indices of heart function were derived from the pressure–length loops obtained during vena cava occlusion. Results In group I, bosentan decreased left ventricular systolic pressure (LVSP) and mean aortic pressure (MAP) dose dependently, reaching 21% and 23% respectively at B4 (LVSP from 190 ± 8 to 150 ± 5 mmHg, P < 0.001; MAP from 167 ± 7 to 128 ± 5 mmHg, P < 0.001). These effects were only related to peripheral vasodilatation, without depression of myocardial contractility, as systemic vascular resistance dropped (from 670 ± 83 to 446 ± 53 mmHg mL −1 min −1 × 10 4 ; P < 0.05), and the end‐systolic pressure–length relationship (ESPLR) remained unchanged (4.0 ± 0.4 vs. 4.3 ± 0.7 mmHg mm −1 kg −1 ). Concomitantly with pressure decline, heart rate tended to increase in this group (from 150 ± 4 to 156 ± 6 beats min −1 ). When autonomic system was blocked (group II), administration of bosentan induced similar hypotensive effects as in group I (26% and 28% reduction in LVSP and MAP respectively, P < 0.001) whereas ESPLR did not change (3.0 ± 0.9 vs. 3.1 ± 0.5mmHg −1 mm kg −1 ). Under these sympathetically blocked conditions, heart rate significantly fell after bosentan infusion (from 120 ± 4 to 110 ± 6 beats min −1 , P < 0.001). Conclusions Without influencing heart function, bosentan is an efficient and safe therapy that opens up new therapeutic perspectives in human essential hypertension.