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Biomedical subjects

K D Bock

Publications and source records attributed to K D Bock.

At least 37 records · Page 2Linked to original sources
PubMed1986

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.

Adrenergic beta-Antagonists↗
PubMed1986

Intraperitoneal fibrin-formation and its inhibition in CAPD.

The intraperitoneal fibrin formation and its inhibition by intraperitoneal heparin (5000 U) was investigated in six patients on CAPD. The intraperitoneal heparin concentration decreased linearily from 1.78 U/ml to 1.13 U/ml during a 4-hour dwell time. The antithrombin III-concentration increased to 0.56 +/- 0.1 mg/dl, reaching 1.87% of normal plasma values. The antithrombin III-portion of total protein was 0.62% in plasma and 0.79% in dialysate. The fibrinopeptide A-concentration, a specific product of thrombin action on fibrinogen was 37.1 +/- 11.8 ng/ml in plasma (normal range: less than 2.5 ng/ml) and 153.4 +/- 16.8 ng/ml in dialysate during regular CAPD. After the addition of 5000 U heparin the fibrinopeptide A-concentration in dialysate decreased to 11.6 +/- 2.6 ng/ml during a 4-hour dwell time. In vitro experiments showed no remarkable inhibition of fibrin formation by heparin without antithrombin III in dialysate. We suggest that the fibrinopeptide A is produced intraperitoneally and the antithrombin III-concentration in dialysate is sufficient to inhibit the fibrin formation after acceleration by heparin.

Antithrombin III↗
PubMed1985

Alpha- and beta-adrenoceptors in circulating blood cells of essential hypertensive patients: increased receptor density and responsiveness.

In 40 male patients with established essential hypertension (P diast greater than 95 mmHg) platelet alpha 2-adrenoceptor density (by 3H-yohimbine binding) and -responsiveness (by adrenaline-induced aggregation) as well as lymphocyte beta 2-adrenoceptor density (by (+/-)-125 iodocyanopindolol binding) and -responsiveness (by cyclic AMP responses to isoprenaline) were determined and compared with those in 40 male age-matched normotensives (P diast less than 90 mmHg). In essential hypertensive patients mean platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities were significantly increased. When data from all 80 subjects were combined, significant positive correlations between mean arterial blood pressure and alpha 2- and beta 2-adrenoceptor densities, respectively, were found. The increases in alpha 2- and beta 2-adrenoceptor densities were accompanied by enhanced responsiveness to adrenergic stimulation: in platelets adrenaline-induced aggregation--via alpha 2-adrenoceptor stimulation--was exaggerated, and in lymphocytes isoprenaline produced significantly greater increases in the intracellular level of cyclic AMP. It is concluded that the increased density and responsiveness of alpha 2-and beta 2-adrenoceptors in circulating blood cells of essential hypertensive patients may reflect increased sympathetic activity, which might contribute to the elevation of blood pressure.

Adenylyl Cyclases↗
PubMed1985

Acute regulation of lymphocyte beta 2-adrenoceptors is altered in patients with essential hypertension.

The effects of acute stimulation of the sympathetic activity by dynamic exercise on lymphocyte beta 2-adrenoceptor density [assessed by (-)-125iodocyanopindolol (ICYP) binding] and responsiveness [10 mumol/l isoprenaline-induced cyclic adenosine monophosphate (cAMP) increases] were studied in 10 normotensive (Pdiast < 90 mmHg) volunteers and in 10 patients with established essential hypertension (Pdiast > 95 mmHg). In normotensives, dynamic exercise on a bicycle (80% of maximum heart rate) for 15 min led to an increase in lymphocyte beta 2-adrenoceptor density from 1080 +/- 77 to 2033 +/- 152 ICYP binding sites/cell; concomitantly isoprenaline-induced increase in lymphocyte cAMP was enhanced. This effect appears to be mediated by beta 2-adrenoceptor stimulation, since the exercise-induced increase in beta 2-adrenoceptor density was markedly attenuated by pretreatment of the volunteers with propranolol (5 mg intravenously 45 min before exercise), but not by pretreatment with the beta 1-selective antagonist bisoprolol (2.5 mg intravenously 30 min before exercise). In patients with essential hypertension, lymphocyte beta 2-adrenoceptor density (1512 +/- 101 ICYP binding sites/cell) was significantly higher than in controls (P < 0.05); the same held true for isoprenaline-induced cAMP increases. In these patients, however, dynamic exercise caused only a slight increase in lymphocyte beta 2-adrenoceptor density (to 1859 +/- 154 ICYP binding sites/cell) and in isoprenaline-induced cAMP increases. From these results it is concluded that in essential hypertension acute regulation of the beta-adrenoceptor/adenylate cyclase system is impaired.

Adult↗
PubMed1985

Intraperitoneal heparin in CAPD.

In six patients on CAPD (continuous ambulatory peritoneal dialysis) the systemic effects of intraperitoneally administered heparin (5000 U) were investigated. Using a modification of a plasma heparin determination serial measurements of heparin concentration in dialysate were performed. During a dwell time of 4 hours the intraperitoneal heparin level decreased by 1825 +/- 253 U (mean +/- S.E.M.). Simultaneously the plasma anti-IIa-activity of heparin after 4 hours and the anti-Xa-activity after 2 and 4 hours increased significantly (p less than or equal to 0.05). The maximum of heparin activity after 4 hours was 0.015 +/- 0.001 U/ml and 0.024 +/- 0.003 U/ml, respectively (mean +/- S.E.M.). An increase of activated partial thromboplastin time was not observed. The small increase of heparin activity in plasma is in contrast to reported activities measured after subcutaneous application of this dose of heparin. In CAPD the effect of heparin is largely restricted to the peritoneal cavity.

Female↗
PubMed1984

Changes in platelet alpha 2-adrenoceptors in human phaeochromocytoma.

In a 44 year-old male with a surgically proven phaeochromocytoma platelet alpha 2-adrenoceptor density, determined by 3H-yohimbine binding, was only 50% of that in an age-matched control group, and plasma catecholamines were elevated. Two weeks after removal of the tumour, platelet alpha 2-adrenoceptor density and plasma catecholamines had become normal and were not significantly different from the controls. It is concluded that endogenous catecholamines may play an important role in regulation of alpha 2-adrenoceptor density and hence tissue sensitivity to alpha-adrenergic stimulation in the human being.

Adrenal Gland Neoplasms↗
PubMed1984

Increased density and responsiveness of alpha 2 and beta-adrenoceptors in circulating blood cells of essential hypertensive patients.

In 40 male patients with established essential hypertension (P diastolic greater than mmHg) the density and responsiveness of platelet alpha 2-adrenoceptors and lymphocyte beta 2-adrenoceptors were measured and compared with those in 40 male age-matched normotensive subjects (P diastolic less than 90 mmHg). The mean densities of platelet alpha 2-adrenoceptors (assessed by 3H-yohimbine binding) and of lymphocyte beta 2-adrenoceptors (assessed by (+/-) 125 iodocyanopindolol binding) were significantly increased in essential hypertensive patients (P less than 0.01). If data from all 80 subjects were combined there were significant positive correlations between mean arterial blood pressure of the subjects and alpha 2-adrenoceptor density (r = 0.591, P less than 0.001) and beta 2-adrenoceptor density (r = 0.648, P less than 0.001), respectively. The increases in and beta-adrenoceptor densities in essential hypertension were accompanied by enhanced responsiveness alpha- of platelets to 10 microM adrenaline to adrenergic stimulation: the aggregatory response via alpha 2-adrenoceptor stimulation) was increased, and in lymphocytes isoprenaline (0.01 - 100 microM) produced (via adrenoceptor stimulation) greater increases in cyclic AMP at each concentration than in control. Furthermore, activation of platelet adenylate cyclase by prostaglandin E1 was exaggerated in essential hypertensive patients. It is concluded that the increased density and responsiveness of alpha- and beta-adrenoceptors in essential hypertension may reflect enhanced sympathetic activity, and may contribute to the elevation of blood pressure.

Adolescent↗
PubMed1983

Subclassification of human beta-adrenergic receptors mediating renin release.

To determine the beta-adrenoceptor subtype controlling renin release from the kidneys, several beta-adrenoceptor subtype selective agonists and antagonists were administered to 15 healthy volunteers. While isoprenaline infusion (1, 2 and 4 micrograms/min for 5 min each) markedly increased plasma renin activity (PRA), the beta 2-selective agonist fenoterol failed to change PRA. The isoprenaline induced rise in PRA could be completely prevented by the beta 1-selective antagonists metoprolol (10 mg i.v. 45 min prior to isoprenaline infusion) and betaxolol (5 mg i.v. 45 min prior to infusion) indicating that renin release is mediated by beta 1-adrenoceptors. Binding studies with the highly specific beta-adrenoceptor radioligand (+/-)-125iodocyanopindolol demonstrated that membranes from human kidney cortical slices contain predominantly, if not exclusively, beta 1-adrenoceptors. These in vivo and in vitro results support the view that the beta-adrenoceptor mediating renin release from the human kidney is of the beta 1-subtype.

Adrenergic beta-Agonists↗
PubMed1982

Age-dependent decrease of alpha 2-adrenergic receptor number in human platelets.

In 36 healthy subjects of various ages (14-76 years) the number of alpha 2-adrenergic receptors in platelets - as determined by [3H]yohimbine binding - and plasma catecholamine levels were measured. A highly significant negative correlation (r = -0.666, P less than 0.001) between the number of alpha 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.

Adolescent↗
PubMed1982

GTP regulates binding of agonists to alpha 2-adrenergic receptors in human platelets.

The potent alpha 2-adrenergic receptor antagonist 3H-yohimbine was used to characterize alpha-adrenergic receptors in human platelet membranes. Binding of 3H-yohimbine was at 25 degrees rapid (t 1/2 = 3 min) readily reversible (t 1/2 = 5.5 min), saturable with 221 +/- 38.9 fmoles bound/mg protein (N = 10) and of high affinity (KD = 1.97 nM). Inhibition of binding by alpha-adrenergic antagonists showed monophasic displacement curves with Hill-coefficients of approximately 1.0. The rank order of potency was: rauwolscine greater than or equal to yohimbine greater than phentolamine greater than phenoxybenzamine greater than AR-C 239 greater than or equal to corynanthine greater than prazosin, indicating that the alpha-adrenergic receptor in human platelets is of the alpha 2-subtype. On the contrary, agonist (clonidine, guanfacine, alpha-methyl-noradrenaline, noradrenaline and adrenaline) displacement curves were shallow with Hill-coefficients of approximately 0.7. Non-linear regression analysis showed that agonists bind to two affinity states of the alpha 2-adrenergic receptor, a high and a low affinity state. In the presence of GTP (10(-4) M) agonist concentration-inhibition curves were shifted to the right to lower affinities and Hill-coefficients increased up to 1.0 K1-values for inhibition of binding in the presence of GTP were in the same range as those for low affinity state in the absence of GTP. It is concluded that GTP regulates binding of alpha 2-adrenergic agonists at the human alpha 2-adrenergic receptor.

Adrenergic alpha-Agonists↗