ALTERED BETA-ADRENERGIC-RECEPTOR FUNCTION IN SUBJECTS WITH SYMPTOMATIC MITRAL-VALVE PROLAPSE

Individuals with mitral valve prolapse (MVP) frequently show symptoms of a hyperadrenergic state. Beta-adrenergic receptor characteristics were compared in the lymphocytes of subjects with symptomatic MVP and control subjects during rest and exercise. At rest, the proportion of receptors binding agonist with high affinity, as determined from isoproterenol competition for (-)[I-125]-iodopindolol binding sites, was greater in MVP subjects than in controls. With exercise, the proportion of high-affinity receptors in MVP subjects decreased to control levels. Isoproterenol stimulation of lymphocyte 3',5'-cyclic adenosine monophosphate (cyclic AMP) also was greater in MVP subjects than in controls at rest, but not during exercise. Plasma catecholamine concentrations in MVP subjects were normal during both rest and exercise. Unlike exercise, isoproterenol infusion elicited clinical manifestations of increased adrenergic responsiveness in MVP subjects. The beta-receptor in exercised MVP subjects exhibited unusually high affinity agonist binding (i.e. a lower dissociation constant K(H) than in either the same subjects at rest or exercised controls) and also abnormal coupling to the stimulatory guanine nucleotide-binding regulatory protein (G(S)) of adenylate cyclase, as reflected by the inability of guanine nucleotide to convert the receptor to a low-affinity state. These findings suggest that functional alteration of the beta-adrenergic receptor, in the absence of abnormal plasma catecholamine levels, might contribute to the hyperadrenergic state of MVP subjects at rest. However, desensitization of high affinity beta-receptors or altered receptor-G(S) coupling might preserve normal adrenergic responsiveness during exercise.