Adrenergic cardiovascular control before and after removal of stimulatory α-1 adrenoreceptor antibodies.

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. Agonistic autoantibodies directed against G protein– coupled receptors are implicated in the pathogenesis of various human cardiovascular disorders. A patient subset with idiopathic dilated cardiomyopathy features agonistic antibodies directed against ␤-1 adrenoreceptors. Subsequently, immunization against ␤-adrenore-ceptors in rats, as well as transfer of serum to nonimmunized animals, induces left ventricular dilation and dysfunction. 1 Ag-onistic antibodies against the angiotensin II subtype 1 receptor may contribute to preeclampsia and humorally mediated kidney transplant rejection. More recent studies identified agonistic antibodies against the ␣-1 adrenoreceptor in 51% of treatment-resistant hypertension patients. 2 In vitro, patient and rabbit ␣-1 adrenoreceptor antibodies activated protein kinase C-␣ and transient extracellular-related kinase phosphorylation and induced mesentery artery segment contraction. 2 Finally, 5 patients in whom agonistic ␣-1 adrenoreceptor antibodies were removed through immunoabsorption showed favorable blood pressure responses. 2 Another study arrived at similar conclusions after infused antibodies rapidly raised blood pressure in anesthetized rats; prazosin abolished the response. 3 However, how agonistic ␣-1 adrenoreceptor antibodies might affect cardiovascular adren-ergic regulation in humans is unknown. To address this issue, we tested responses to physiological sympathetic nervous system stimuli and exogenous adrenergic agonists before and after immune absorption. We studied 5 patients (4 men and 1 woman; 58Ϯ4 years; 31Ϯ2 kg/m 2) with treatment-resistant arterial hypertension and agonistic ␣-1 adrenoreceptor antibodies whose office blood pressure data have been included in a previous report. 2 Patients received no antiadrenergic medications. All of the other antihy-pertensive medications were kept constant throughout the study. Patients underwent immune adsorption on 5 consecutive days. At each session, the calculated plasma volume was passed through adsorption columns at 50 mL/min. Levels of antibodies against the ␣ 1-adrenergic receptor were measured by a bioassay using spontaneously beating rat cardiomyocytes. Immune adsorption substantially reduced ␣-1 adrenoreceptor autoantibodies (24Ϯ1 ⌬bpm/min before versus 5Ϯ1 ⌬bpm/min after immune adsorp-tion; PϽ0.001). Before and 5 to 12 days after immune adsorp-tion, we conducted a battery of autonomic function tests and sensitivity testing with incremental intravenous phenylephrine and nitroprusside doses. ECG and beat-by-beat finger blood pressure (Finapres) were continuously recorded. Brachial blood pressure was monitored to assess absolute blood pressure levels (Dinamap). The local ethics committee approved the study, and written-informed consent was obtained. All data are expressed as meanϮSEM. Before …