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Density and binding characteristics of beta‐adrenoceptors in the normal and failing equine myocardium
Author(s) -
HORN J.,
BAILEY S.,
BERHANE Y.,
MARR C. M.,
ELLIOTT J.
Publication year - 2002
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.2746/042516402776249056
Subject(s) - medicine , endocrinology , antagonist , heart failure , beta (programming language) , population , alpha (finance) , receptor , chemistry , biology , construct validity , nursing , environmental health , computer science , patient satisfaction , programming language
Summary Beta‐adrenoceptors are important regulators of cardiac function and their characteristics are known to chagne in human and canine diseased myocardium. This study aimed to determine the density and subtypes of beta‐adrenoceptors in the normal and failing equine ventricular myocardium. Membrane preparations of the left papillary muscles were incubated with increasing concentrations of the nonselective beta‐adrenoceptor antagonist [ 3 H]‐CGP12177. Saturable and reversible binding of [ 3 H]‐CGP12177 to myocardial membranes was demonstrated with K d values (± s.d.) of 0.49 ± 0.40 and 0.43 ± 0.22 nmol/l and B max values of 93.4 ± 20.5 and 110.0 ± 21.2 and fmol/mg protein for normal (n = 19) and heart failure (n = 10) tissues, respectively. Heart failure had no significant effect on the density of ventricular beta‐adrenoceptors. The cardiac beta‐adrenoceptors were further characterised by studying displacement of [ 3 H]‐CGP12177 (0.6 nmol/l) with the beta 1 ‐selective antagonists CGP20712A and the beta 2 ‐selective antagonist ICI118.551. In normal ventricular muscle, CGP20712A was 26 times more potent than ICI118.551 (K i values 30.4 ± 24.8 and 814.1 ± 485.2 nmol/l, respectively). In heart failure cases, CGP 20712A curves were monophasic with a K i value of 45.6 ± 39.7 nmol/l. ICI 118.551 curves were biphasic in 5 horses where 11–31% of the cardiac beta‐adrenoceptors had a high affinity for ICI 118.551. These data suggest that the normal equine ventricular myocardium possesses predominately beta 1 ‐adrenoceptors, with no evidence for co‐existence of a significant population of beta 2 ‐adrenoceptors. The density of beta‐adrenoceptors did not appear to change in heart failure, but the appearance of receptors with a high affinity for ICI118.551 may suggest that, in some cases, heart failure increases the expression of beta 2 ‐adrenoceptors in equine ventricular myocardium. This study provides an insight into the role of the adrenergic system in heart disease in the horse. Further studies in this area are warranted.