Adrenaline and noradrenaline as possible chemical mediators in the pathogenesis of arteriosclerosis.

We studied the relationships between adrenaline and noradrenaline and factors associated with arteriosclerosis to determine whether catecholamines contribute to the atherogenetic process. We investigated the effects of adrenaline and noradrenaline on cultures of vessel wall cells from rats and analyzed plasma catecholamine levels in humans exposed to atherogenic risk factors, undergoing hemodialysis treatment or following myocardial infarction or stroke. I.

A possible role of catecholamines in atherogenesis and subsequent complications of atherosclerosis.

Cultured smooth muscle cells (SMC) from rat aorta and endothelial cells (EC) from pig aorta were used to study the effect of the catecholamines epinephrine and norepinephrine on cell proliferation. Both stimulated growth of SMC and EC when added to the culture medium. Besides epinephrine and norepinephrine, dopamine and some of their metabolites also stimulated proliferation of cultured endothelial cells.

[A single, rapid, selective and quantitative determination of adrenaline and noradrenaline in the plasma by a combination of solvent extraction, HPLC separation and electrochemical detection].

A very simple and rapid solvent extraction system for the selective and quantitative isolation of epinephrine and norepinephrine from plasma is described. The extraction system makes use of the complex formation in alkaline medium between diphenylborate and the diol group of the catecholamines in combination with ion-pair formation. The extraction procedure, in conjunction with HPLC-separation and electrochemical detection, allows the quantitative determination of epinephrine and norepinephrine from plasma.

Connective tissue proteins on the injured endothelium of the rat aorta.

Type V collagen (TVC), fibronectin (FN), and laminin (LAM) were detected on the endothelial surface of mechanically injured rat aortas with the help of monospecific antisera and protein A - gold conjugates, carbon film surface replicas, and conventional embedding techniques. Deendothelialized tracks were produced in the thoracic aorta, and the presence of the connective tissue proteins on the luminal surface of the endothelium was studied. The changes in the distribution of the proteins during repair of the endothelial surface was followed for up to 6 days after injury.

About the effect of risk factors on the structure and the proliferation of arterial wall cells. Part 2: Changes in structure and proliferation of cultivated aortic endothelial cells from hypertensive minipigs.

Cultured aortic endothelial cells (EC) from normotensive and hypertensive minipigs were studied in the second passage. Cytological measurements performed on confluent cultures of the same age in the second subculture revealed significant smaller surface areas and circumferences of EC and of their nuclei in the hypertensive group compared to those in the normotensive control group. The percentage of polynuclear EC was higher in cultures from hypertensive animals than in cultures from normotensive ones.

About the effect of risk factors on the structure and the proliferation of arterial wall cells. Part 1: Changes in structure and proliferation of cultivated aortic smooth muscle cells from hypertensive-diabetic rats.

In cultivated aortic smooth muscle cells (SMC) from normal or hypertensive-diabetic rats respectively, two types of cells, small SMC and large ones, were observed. The differences between the surface areas, form factors and nucleus-plasma relations of the small and the large cells, measured by morphometric methods are evident. The ratio of small to large cells originating from the normal group was 87%: 13%, and of those originating from the hypertensive-diabetic group 76%: 24%.

[Pathogenesis of coronary sclerosis].

It should first be pointed out that all arterial wall cells are mesenchymal cells, and that arteriosclerosis is a reactive disease of the arterial wall. A huge amount of different pathological factors is capable of inducing a reaction of arterial wall cells in the context of the "unspecific mesenchymal reaction". The reaction of the arterial wall cells to the influence of these factors is a biological process occurring as a complicated event of induction and reaction.

Cultivated human arterial smooth muscle cells. The effect of donor age, blood pressure, diabetes and smoking on in vitro cell growth.

The growth capacity and morphology of cultured human smooth muscle cells obtained from omental arteries from 153 patients were studied. The cells exhibited a very slow growth rate compared to rat or minipig SMC's, but they too developed cultures in a typical hill-and-valley pattern and possessed bundles of myofilaments. Two groups of smooth muscle cell cultures, slowly proliferating ones and rapidly proliferating ones were compared in their relation to donor age, blood pressure, nicotine abuse, diabetes mellitus and carcinoma.

Special characteristics of cultured smooth muscle cell subtypes of hypertensive and diabetic rats.

In rat smooth muscle cell cultures two types of cells were detected. The majority of cells were small and spindle-shaped, 15% of which were labeled with H3-thymidine and displayed a nucleus/plasma relation of 1:15. Thirteen percent of the smooth muscle cell population was large and partly polynuclear.

[Physiology and physiopathology of aging].

First of all some information will be given on history, methods and the actual situation of the research in aging. Aging ist not a disease but a physiologic process characterized by growth and maturity events which legally change the functional performances and the anatomical structures of the human beings in time. This aging trend depends on the metabolism of the living cells whose metabolism changes over the years.

Growth rate differences between arterial smooth muscle cells cultivated from rat impaired by short--or long--term hypertension respectively.

In former studies short-term renal hypertension (2 weeks) in rats led to a remarkable increase of arterial smooth muscle cells (ASMC) proliferation in cultures and subcultures, examined by cell counting and 3H-thymidine indices /flasks in cultures or subcultures of hypertensive rats. The activated cell growth was observed up to the 6th subcultures. The proliferation of ASMC cultivated from short-term hypertensive rats is suppressed or eliminated respectively by antirheumatic drugs up to the 6th subcultures.

Effect of risk factors and antirheumatic drugs on the proliferation of aortic wall cells.

The proliferation of aortic smooth muscle cells (ASMC) of Wistar rats, impaired by risk factors such as arterial hypertension, diabetes mellitus, atherogenic diet and staphylolysin injections and of normal Wistar rats treated with antirheumatic drugs such as prednisolone and acetylsalicylic acid was investigated. The cells of these animals were cultivated, subcultivated, and in the 2nd subcultures the cell numbers/5 ml medium were counted by means of Coulter Counter, and the cells were incubated with [3H]thymidine and the percentage of labelling in 100 or 1000 counted cells was stated. The effect of risk factors such as LDL and staphylolysin and of antirheumatic drugs such as prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine added to the 2nd subcultures of cultivated ASMC of normal minipigs was investigated by the same method.

[The effect of pathogenic factors and anti-rheumatic drugs on the proliferation of cultured human fibroblasts].

1. Staphylolysin and low density lipoprotein (LDL) stimulate the proliferation of cultivated fetal human fibroblasts of the lung. 2.

DNA template activity in the arterial wall of hypertensive rabbits.

With a new method employing acridine organe (AO) as an ultracytochemical probe DNA template activity could be visualized within cell nuclei of the thoracic aortic wall of rabbits. After experimentally produced chronic renal hypertension nuclei with a relatively high number of AO chromatin interaction products were found in the endothelium, in the intimal region, in the outer third of the media, and in the adventiia indicating increased DNA template activity. This representative distribution pattern of DNA template activity was not found in comparable regions of the thoracic aorta of normotensive rabbits.

[Prevention and therapy of arteriosclerosis (author's transl)].

Arteriosclerosis is caused by many factors. These pathogenic factors especially over-nutrition, nicotinabusus, deficiency of muscular exercise, muscular overstrain, emotional stress and concomitant basic diseases, especially arterial hypertension, diabetes mellitus and dyslipidemia are the most important points for preventive and therapeutical action. When possible the risk factors has to be eliminated, arterial hypertension, diabetes mellitus and dyslipidemia have to be treated orderly.

[Correlations between age, risk factors for arteriosclerosis and endocrine functions (author's transl)].

In 377 males and 528 female factory workers basal serum levels of glucose, neutralfat, cholesterol, Na, K, Ca and LH, FSH, TSH, Prolactin, GH, Insulin, total corticoids and testosteron were determined. Mean values and standard deviations as well as correlations between mean basal hormone levels and other serum parameters, blood pressure and relative body weight (Broca Index) and partial correlations excluding age and relative body weight were calculated. Basal serum levels of LH, FSH, GH and prolactin show age and sex dependent secretion patterns.