ISSN:
1432-1912
Keywords:
Key words: β-Adrenoceptors
;
Force of contraction
;
Human myocardium
;
Hypertrophy
;
Mitral regurgitation
;
Adrenaline
;
Noradrenaline
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Only few data are available concerning the biochemical and functional state of the β-adrenergic system in hypertrophied human myocardium. The present study was to investigate the myocardial β-adrenergic signal transduction system in hypertrophic obstructive cardiomyopathy (HOCM). Thin myocardial strips were prepared from surgically excised, septal myocardium from 7 patients with HOCM and their force of contraction was measured in vitro. The positive inotropic effects of calcium and dihydro-ouabain, both acting independently of β-adrenoceptors and cAMP, were similar in these preparations to those, previously published, seen with nonfailing myocardium. In contrast, the β-adrenoceptor agonist isoprenaline and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) had reduced positive inotropic effects. Their EC50-values were about 10 fold higher than the respective EC50-values published for nonfailing myocardium. The positive inotropic potencies of isoprenaline and IBMX were reduced in HOCM by as much as they were in the additionally investigated myocardium from 6 patients with severe mitral regurgitation (MR, NYHA III). In order to clarify whether the functional alterations are related to changes in the β-adrenoceptors, β-adrenoceptor density and β1:β2-adrenoceptor subtype distribution were determined in the same myocardium using 125I-Iodocyanopindolol saturation binding. Myocardial β-adrenoceptor density was reduced to 68% in HOCM and to 56% in MR compared to nonfailing myocardium controls (NF: 64.8±6.5 fmol/mg protein). In HOCM, this reduction was due to a selective down regulation of β1-adrenoceptors (24.9±3.7 fmol/mg protein vs NF: 46.4±6.8 fmol/mg protein, P〈0.05), whereas β2-adrenoceptor density was unchanged (19.0±1.9 fmol/mg protein vs NF: 18.4±3.3 fmol/mg protein, n.s.). In MR both β-adrenoceptor subtypes were reduced (β1: 26.9±1.4 fmol/mg protein, β2: 9.6±1.7 fmol/mg protein; both P〈0.05 vs NF). Electrochemically determined plasma catecholamine levels were elevated in MR. However, plasma catecholamine levels were normal or slightly below normal in HOCM. In summary, myocardial β-adrenoceptors are downregulated and their function is impaired in HOCM. This desensitization is not caused by a negative feedback regulation due to increased plasma catecholamines. The present results show that the desensitizations of the β-adrenergic system associated with HOCM has characteristics that indicate a major deviation in its development from that of the β-adrenergic desensitization previously described to occur in congestive heart failure.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169081
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