Reduction In Angiotensin-converting Enzyme Activity Research Articles

Hormonal influence on endothelial cell angiotensin-converting enzyme activity.

The influence of various hormones on angiotensin-converting enzyme (ACE) production and release by bovine endothelial cells in culture was studied. Dexamethasone, thyroxine (T4), and triiodothyronine (T3) stimulated ACE activity in cells and their culture supernatants without affecting cell number or protein content. The stimulating effects of dexamethasone and thyroid hormones were additive, suggesting that these hormones may have different sites of action. In addition, their stimulating effects were blocked by cycloheximide, indicating that increased enzymatic activity occurred through new protein synthesis. The exposure of cells to insulin reduced ACE activity of cells and their culture supernatants without influencing cell counts or protein content; insulin also partially inhibited the stimulation of ACE activity by dexamethasone or T3. Our studies suggest that the production of ACE by endothelial cells is under hormonal regulation. Release of ACE activity into culture supernatants parallels changes in cellular ACE activity. The results supplement previous observations made in vitro and in vivo.

Effect of prolonged exercise at altitude on the renin-aldosterone system.

The combined effect of exercise and altitude on the renin-aldosterone system was studied in six male subjects on a fixed diet. After 4 control days at rest and at low altitude, subjects ascended to 3,100 m and took about 7 h exercise daily for 5 days. There followed a 4-day recovery period at low altitude. Daily blood samples were taken for estimation of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and angiotensin converting-enzyme (ACE) activity. Results showed a maximal rise in PRA and PAC with exercise at altitude maximal on the first 2 days. ACE activity fell by 23% at altitude. Compared with similar exercise at sea level, the rise in PAC was comparable but the rise in PRA was four times greater, indicating a marked decrease in PAC response to PRA. It is suggested that this loss of sensitivity of PAC to PRA is mediated by the measured reduction in ACE activity.

Reduced activity of angiotensin-converting enzyme in basal ganglia in early onset schizophrenia.

SYNOPSISThe dipeptidyl peptidase, angiotensin-converting enzyme (EC 3.4.15.1), was measured in various regions of post-mortem brains. Results from 51 patients with the hospital diagnosis of schizophrenia who were divided into the clinical categories of ‘schizophrenia’ and ‘schizophrenialike’ illness on the basis of case-note analysis were compared with those from 40 control subjects. A significant reduction in angiotensin-converting enzyme activity was observed only in the substantia nigra pars reticulata and in the lateral and medial segments of globus pallidus in the ‘schizophrenia’ group, with no significant differences in enzyme activity in substantia nigra pars compacta, caudate nucleus, nucleus accumbens, subthalamic nucleus or cerebellar cortex. Reduced enzyme activity was not seen in the ‘schizophrenia-like’ group, and occurred most significantly in ‘schizophrenia’ patients in whom the onset of the illness had occurred between the ages of 15 and 24 years. In the control population the activity of angiotensin-converting enzyme in substantia nigra pars reticulata decreased significantly with age. It is possible that patients with early onset ‘schizophrenia’ may represent a separate disease entity, rather than belonging to a spectrum of a single disease.

Angiotensin-converting enzyme in substantia nigra: Reduction of activity in huntington's disease and after intrastriatal kainic acid in rats

The substantia nigra of Huntington's disease brains shows a 78% reduction in angiotensin-converting enzyme activity in the pars reticulata and a 48% reduction in the pars compacta. The nucleus accumbens shows a 29% reduction in converting enzyme activity. In the rat, after instrastriatal injections of kainic acid 92.5 μg), an agent which selectively destroys neuronal cell bodies, there is a 55% reduction in angiotensin-converting enzyme activity in the ipsilateral substantia nigra. Both human and animal data suggest that a major part of the angiotensin-converting enzyme in the substantia nigra is localized in nerve terminals whose cell bodies originate in the striatyum.