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Role of endothelin‐1 receptors in healthy anaesthetized rabbits
Author(s) -
SchmitzSpanke S,
Schipke JD
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03500.x
Subject(s) - endothelin receptor , vasomotion , chemistry , medicine , aortic pressure , receptor , bolus (digestion) , heart rate , cardiac function curve , ventricular pressure , mean circulatory filling pressure , vascular resistance , endocrinology , hemodynamics , cardiac output , blood pressure , vasodilation , heart failure , central venous pressure
SUMMARY 1. Many diseases are associated with elevated endothelin (ET)‐1 plasma concentrations. In order to understand the consequence of this elevation, in the present study the effects of exogenous ET‐1 on the entire organsim were investigated, in particular with respect to the role of ET A and ET B receptors in the cardiovascular system. In open‐chest rabbits, left ventricular (LV) pressure (LVP max , LVP ed ), dP/dt max and dP/dt min were recorded in ejecting and isovolumically beating hearts to determine cardiac function. In addition, heart rate (HR), aortic pressure (AoP) and aortic flow (AoF) were measured. Total peripheral resistance (TPR) was calculated from mean AoP and AoF. 2. In the first series of experiments ( n = 11), ET‐1 (0.5 nmol/kg; bolus) produced a non‐significant reduction in HR. Systolic function, in terms of AoF, LVP max and dP/dt max , was improved; for example, LVP max was increased significantly (69 ± 10 vs 106 ± 20 mmHg for control and ET‐1, respectively; P < 0.05). Similarly, early relaxation (dP/dt min ) was improved. In parallel, TPR rose significantly (0.25±0.07 vs 0.35±0.1 mmHg/min per mL for control and ET‐1, respectively; P < 0.05). Isovolumic measurements showed corresponding responses. 3. In the second series of experiments ( n = 7), animals were pretreated with an ET A receptor antagonist (330 nmol/min per kg FR 139317). After ET A receptor blockade, the administration of ET‐1 had no significant effect on cardiac function or vasomotion. 4. In the third series of experiments ( n = 6), animals were pretreated with an ET B receptor antagonist (10 nmol/min per kg BQ 788). In this series of experiments, the effects of ET‐1 on cardiac function and vasomotion were the same as in the first series of experiments, except for the effect on HR, which decreased by 35% after ET‐1. 5. In our experimental model, exogenous ET‐1 exerted a clear‐cut positive inotropic effect, together with the anticipated peripheral vasoconstriction via ET A receptors.