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Altered beta adrenergic receptor function in subjects with symptomatic mitral valve prolapse.
1Department of Medicine, Audie L. Murphy Memorial Veterans Hospital, Texas 78284.
The American Journal of the Medical Sciences
|August 1, 1991
Summary
Mitral valve prolapse (MVP) patients exhibit a hyperadrenergic state due to altered beta-adrenergic receptors. These receptors show increased high-affinity binding at rest, normalizing with exercise, suggesting a functional receptor abnormality.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Individuals with mitral valve prolapse (MVP) often present with symptoms indicative of a hyperadrenergic state.
- The role of beta-adrenergic receptor characteristics in the hyperadrenergic state associated with MVP requires further elucidation.
Purpose of the Study:
- To compare beta-adrenergic receptor characteristics in lymphocytes of symptomatic MVP subjects and controls at rest and during exercise.
- To investigate the functional coupling of beta-adrenergic receptors to adenylate cyclase in MVP subjects.
Main Methods:
- Lymphocyte isolation from MVP and control subjects at rest and after exercise.
- Measurement of beta-adrenergic receptor affinity using isoproterenol competition for (-)[125I]-iodopindolol binding.
- Assessment of isoproterenol-stimulated cyclic AMP production and guanine nucleotide-mediated receptor affinity conversion.
Main Results:
- At rest, MVP subjects showed a higher proportion of high-affinity beta-adrenergic receptors and greater isoproterenol-stimulated cyclic AMP production compared to controls.
- During exercise, the proportion of high-affinity receptors in MVP subjects decreased to control levels, and cyclic AMP response normalized.
- Isoproterenol infusion elicited increased adrenergic responsiveness in MVP subjects, with evidence of abnormal beta-receptor-GS protein coupling during exercise.
Conclusions:
- Functional alterations in beta-adrenergic receptors, not plasma catecholamine levels, may contribute to the hyperadrenergic state in MVP subjects at rest.
- Desensitization of high-affinity beta-receptors or altered receptor-guanine nucleotide-binding protein (GS) coupling might explain preserved adrenergic responsiveness during exercise in MVP.