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Characterization of lymphocyte β‐adrenoceptor activity and G s ‐protein in patients with rheumatic heart valvular disease
Author(s) -
Dzimiri N.,
Hussain S.,
Moorji A.,
Prabhakar G.,
Bakr S.,
Kumar M.,
Almotrefi AA,
Halees Z.
Publication year - 1995
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1995.tb00512.x
Subject(s) - chronotropic , medicine , iodocyanopindolol , pressure overload , endocrinology , lymphocyte , radioimmunoassay , catecholamine , ventricular pressure , heart disease , population , norepinephrine , chemistry , hemodynamics , blood pressure , heart rate , heart failure , receptor , dopamine , intrinsic activity , cardiac hypertrophy , environmental health , agonist
Summary— In order to test whether the β‐adrenoceptor activity in rheumatic heart valvular disease depends on the ventricular load conditions, we determined their density and binding affinity to [ 125 I]‐iodocyanopindolol in lymphocytes, as well as plasma catecholamine and cAMP levels in 69 patients with regurgitant and stenotic lesions of the aortic and mitral valves. The patients were classified as having left ventricular pressure overload (LVP), left ventricular volume overload (LVV), mixed lesions (MOL) or right ventricular pressure overload (RVP). The β‐adrenoceptor activity was determined by radioligand binding methods, catecholamines by high performance liquid chromatography using an electrochemical detector and cAMP by radioimmunoassay. The mean β‐adrenoceptor density (B max ) of the control group was 60.1 ± 9.5 /mol ( n = 29) per 10 6 lymphocytes. In the study population, the density was decreased by 83% in LVP, 78% in LVV, 87% in MOL and 86% in RVP. Plasma norepinephrine was elevated by 89% in LVP and 60% in MOL, epinephrine by 43% in LVP, 50% in VOL, 115% in MOL and 20% in RVP, while dopamine was not significantly changed, and cAMP was slightly elevated in all four groups. Screening for activating mutational changes in the G sα ‐protein gave negative results, possibly dissociating the elevation in plasma cAMP from stimulatory effects of such abnormalities in the G s ‐protein signaling. These results show a significant attenuation in lymphocyte β‐adrenoceptor density of patients with rheumatic heart valvular disease, irrespective of the type of the prevailing ventricular load conditions. The reduction in receptor density is accompanied by a significant increase in plasma norepinephrine levels in patients with a left ventricular pressure overload and epinephrine in those with volume overload.