No abstract

Alterations in the status or in the regulation of adrenoceptors may contribute to essential hypertension. This could be studied using the recently introduced radio-ligand binding techniques to characterize the adrenoceptors on human peripheral blood cells. The present study shows that patients with essential hypertension have a twofold increase of beta 2-adrenoceptor density on intact mononuclear cells as compared to normotensive controls: 859 +/- 260 (n = 10) vs. 420 +/- 119 (n = 10) maximal binding sites for (+/-) 125-Iodocyanopindolol expressed as molecules per cell (P less than 0.001). Furthermore, there is a highly significant correlation (r = 0.86) between the calculated mean arterial blood pressure and the beta 2-adrenoceptor density over a wide range of normal and increased blood pressure. These findings could only be demonstrated with intact mononuclear cells but not with membrane fractions. No difference was found in receptor affinity between patients with essential hypertension and normotensive controls. Thus, essential hypertension is combined with a higher beta 2-adrenoceptor density on intact mononuclear cells which might represent, for example, an increased density of prejunctional beta 2-adrenoceptors. Mean arterial blood pressure is positively correlated with beta 2-adrenoceptor density over a wide range of blood pressure in normotensives and hypertensives. The expression of beta 2-binding sites on the cell surface is possibly altered in essential hypertension resulting in a disparity between intracellular and extracellular binding sites as compared with normotensives.

No abstract

Saturation experiments were performed on intact human peripheral mononuclear leucocytes (MNL) and MNL membranes with (-)125Iodocyanopindolol (125ICYP) over a large concentration range (1.5-600 pmol/l). The corresponding Scatchard plots were curvilinear suggesting two saturable classes of binding sites: A high affinity binding site (Bmax1 = 1000 +/- 400 sites/cell, Kd1 = 2.1 +/- 0.9 pmol/l for intact MNL and Bmax1 = 550 +/- 190 sites/cell, Kd1 = 4.1 +/- 0.9 pmol/l for MNL membranes) and a low affinity binding site (Bmax2 = 9150 +/- 3590 binding sites/cell, Kd2 = 440 +/- 50 pmol/l for intact MNL and Bmax2 = 11560 +/- 4690 sites/cell, Kd2 = 410 +/- 70 pmol/l for MNL membranes). Dissociation of (-)125ICYP from MNL was biphasic consisting of a slow dissociating component (dissociation rate constant k-1 = (0.5 +/- 0.2) X 10(-3) min-1 for intact MNL and k-1 = (1.0 +/- 0.1) X 10(-3) min-1 for MNL membranes) and a fast dissociating component (k-2 = (80 +/- 20) X 10(-3) min-1 for intact MNL and k-2 = (60 +/- 10) X 10(-3) min-1 for MNL membranes). In dissociation experiments started after equilibration with various (-)125ICYP concentrations k-1 and k-2 were independent of the equilibrium concentration, whereas the percentual occupancy of the slow and the fast dissociating component varied and was similar to the estimated fractional occupancy of either binding site at the same (-)125ICYP concentrations in saturation experiments. The association rate constant was in the same order of magnitude for both binding sites. These results suggest two independent classes of binding sites for (-)125ICYP on MNL.

The effect of an acute endogeneous catecholamine stimulation on the regulation of lymphocyte beta-adrenoceptor activity was studied in a patient with pheochromocytoma. Baseline blood pressure, heart rate, adrenoceptor density, and plasma concentrations of epinephrine, norepinephrine, and cyclic adenosine monophosphate were normal. Excessive spontaneous increases of catecholamine concentrations were accompanied by a rise in blood pressure, bradycardia, and an acute up-regulation of beta-adrenoceptors. Plasma concentrations of cyclic adenosine monophosphate paralleled the increase in receptor density and blood pressure. After normalization of catecholamine plasma levels, blood pressure, and beta-adrenoceptor density returned to baseline values. This observation adds support to the theory that an acute catecholamine stimulation leads to an acute sensitization of the beta-adrenoceptor-adenylatecyclase-cyclic-adenosine-monophosphate system leading to blood pressure elevation.