Klaus Dietrich Bock

Age-dependent decrease of α2-adrenergic receptor number in human platelets

In 36 healthy subjects of various ages (14–76 years) the number of α 2 -adrenergic receptors in platelets — as determined by [ 3 H]yohimbine binding — and plasma catecholamine levels were measured. A highly significant negative correlation (r= −0.666, P 2 -adrenergic receptors and age was found; on the contrary, plasma catecholamine concentrations increased with increasing age. Thus, reduced responses in the elderly to adrenergic stimuli may be due to reduced number of adrenergic receptors.

Correlation between lymphocyte β2-adrenoceptor density and mean arterial blood pressure: elevated β-adrenoceptors in essential hypertension

In 41 normotensive volunteers (diastolic pressure, <90 mm Hg) the β2-adrenoceptor density in lymphocytes was determined by (±)-125iodocyanopindolol (ICYP) binding and compared with that in nine patients with borderline hypertension (diastolic pressure, 90–95 mm Hg) and 45 patients with established essential hypertension (diastolic pressure, >95 mm Hg). The mean number of β2-adrenoceptors for controls was 774 ± 49 (range, 300–1,500) ICYP binding sites/cell. In borderline hypertension it was significantly higher, with 1,037 ± 22 (range, 950–1,150) sites/cell, and increased further in patients with essential hypertension to 1,424 ± 72 (range, 700–2,700) sites/cell. The KD values for ICYP, however, were nearly the same in all groups (∼50 pM). Calculation of the data of all 95 subjects resulted in a significant positive correlation between β2-adrenoceptor density and mean arterial blood pressure (r = 0.637; p < 0.001). Since the properties of β2-adrenoceptors in human lymphocytes resemble those in other tissues, the hypothesis is presented that the increased density of β2-adrenoceptors may reflect sympathetic hyperactivity in essential hypertension, which might contribute (perhaps via enhanced release of endogenous noradrenaline through stimulation of presynaptic β2-adrenoceptors by adrenaline) to the elevation of blood pressure.

Alpha- and beta-adrenoceptors in hypertension. II. Platelet alpha 2- and lymphocyte beta 2-adrenoceptors in children of parents with essential hypertension. A model for the pathogenesis of the genetically determined hypertension.

To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one EHT-parent. Both groups did not differ in age, body weight and height, blood pressure, heart rate, plasma catecholamine levels, plasma renin activity (PRA), and lymphocyte beta 2-adrenoceptor density. Platelet alpha 2-adrenoceptor density, however, was in EHT-children significantly higher than in NT-children. In NT-children, platelet alpha 2-adrenoceptors were significantly, inversely correlated with PRA, indicating that they might mirror renal alpha 2-adrenoceptors which inhibitorily regulate renin release. In contrast, in EHT-children PRA was not at all related to platelet alpha 2-adrenoceptors, suggesting an early (even in the normotensive stage) disturbance of the alpha 2-adrenoceptor-mediated regulation in renin release. From these results and those obtained in the experimental rat models of acquired hypertension, a model for the pathogenesis of the genetically determined hypertension is proposed in which a very early step in the development of hypertension is a genetically determined increase in renal alpha-adrenoceptors that causes enhanced sodium retention. This initiates a chain of events that finally results in increased peripheral vascular resistance and, hence, blood pressure. On the other hand, beta-adrenoceptor changes seem to be secondary phenomena due to the elevation in blood pressure.

Differential changes in lymphocyte beta 2-adrenoceptor density by beta-blocker administration: role of intrinsic sympathomimetic activity.

To study the role of intrinsic sympathomimetic activity (ISA) in beta-blocker-induced changes of beta-adrenoceptors, the effects of administration of several beta-blockers for 9 days on lymphocyte beta 2-adrenoceptor density--assessed by 125iodocyanopindolol binding--were investigated in 47 normotensive volunteers. Propranolol (unselective; no ISA; 4 X 40 mg/day) increased beta 2-adrenoceptor density by 25-40%; after withdrawal beta 2-adrenoceptor density declined slowly, being still elevated for 3 days. In contrast, the unselective beta-blockers pindolol (ISA (isoprenaline = 1.0) = 0.39; 2 X 5 mg/day) and mepindolol (ISA = 0.27; 2 X 5 mg/day) decreased beta 2-adrenoceptor density by 50% and 35%, respectively, while alprenolol with weak ISA (=0.066; 4 X 100 mg/day) had no effect. Among the beta 1-selective blockers studied, celiprolol with ISA (=0.32; 1 X 200 mg/day) decreased beta 2-adrenoceptor density by 30% whereas bisoprolol without ISA (1 X 10 mg/day) had no effect. It is concluded that the ISA determines the direction and amount of beta-adrenoceptor alterations induced by beta-blockers. Furthermore, changes in human lymphocyte beta-adrenoceptors reflect subtype-selective changes in beta 2-adrenoceptors, since the beta 1-selective blocker bisoprolol without ISA--in contrast to propranolol--did not affect lymphocyte beta 2-adrenoceptors. Accordingly, the fact that the beta 1-selective blocker celiprolol with ISA decreased lymphocyte beta 2-adrenoceptors, is consistent with the hypothesis that celiprolol possesses in addition to its beta 1-antagonistic activity a beta 2-agonistic activity.

Urinary enzyme excretion after a single dose of phenacetin and paracetamol (acetaminophen) during antidiuresis and during water diuresis.

2 g phenacetin or paracetamol in a single oral dose were administered to five healthy persons under the conditions of antidiuresis and subsequent water diuresis. Excretion of the brush border enzyme GGT, the cytoplasm enzyme LDH, and the lysosomal enzymes, NAG and GAL, was analysed before, during and after ingestion of the analgesics. Increased excretion of LDH and GGT indicated a similar moderate damage of the tubular epithelia after phenacetin and paracetamol. The state of diuresis appeared to have no influence.

Effects of angiotensin and norepinephrine infusions on total plasma volume and extracellular fluid space in man.

Pressor doses of angiotensin and norepinephrine were infused into normal subjects for 5 to 6 hours. 125I‐human serum albumin space, 82Br space, serum protein concentration, venous hematocrit, blood pressure, and pulse rate were determined at half‐hour intervals before, during, and after the infusions. There were no significant changes in the sizes of 125I‐human serum albumin space, 82Br space, and serum protein concentration during and after the administration of the pressor substances. It is concluded that under the conditions of these experiments angiotensin and norepinephrine cause no detectable water movements into or from the intravascular and extracellular space.