Angiotensin-converting Enzyme Activity Of Endothelial Cells Research Articles

Fucosterol decreases angiotensin converting enzyme levels with reduction of glucocorticoid receptors in endothelial cells

The modulation of angiotensin converting enzyme (ACE) levels was studied using fucosterol, one of phytosterols, in cultured bovine carotid endothelial cells. Addition of fucosterol to the culture medium resulted in the decrease of ACE activity of endothelial cells; however, fucosterol did not directly inhibit ACE activity. Dexamethasone elevated the levels of ACE in normal cells, but this effect was not seen in the fucosterol-treated cells. Receptor assays showed that the amount of glucocorticoid receptors in fucosterol-treated cells decreased to an undetectable level. These results indicate that fucosterol lowers the ACE levels on the endothelial cells by inhibiting the synthesis of glucocorticoid receptors involved in the regulation of ACE levels.

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.

Induction by glucocorticoids of angiotensin converting enzyme production from bovine endothelial cells in culture and rat lung in vivo.

The effect of corticosteroids on angiotensin converting enzyme was investigated in endothelial cell cultures and intact rat lung. Cultured endothelial cells from bovine aorta showed net production of angiotensin converting enzyme (ACE) over 2 d culture in serum-free medium. Dexamethasone (DM) increased cell ACE activity six- to sevenfold at 100 nM with a threshold effect at 0.3 nM. The effect of DM on ACE production was completely inhibited by actinomycin D or cycloheximide. Deoxycorticosterone (DOC) and aldosterone were markedly less active, with a threshold near 100 nM and significant (two to threefold) stimulation of ACE activity at 1 muM. In cells incubated in the presence of 10 nM DM, DOC (10 muM) significantly inhibited ACE production compared with 10 nM DM alone, suggesting that DOC is a partial agonist/partial antagonist in this enzyme system. Protein content of cells or medium was unchanged by steroids at all doses used. In vivo, adrenalectomized rats showed lower pulmonary ACE compared with intact controls, and when injected with DM (40 mug/d for 4 d) showed a significant (twofold, P < 0.002) increase in lung ACE over oil-injected, adrenalectomized controls; serum ACE did not change. Injection with DOC (40 mug/d) or aldosterone (10 mug/d) had no effect on lung or serum ACE. Over a range (0.6 to 2,000 mug) of concentrations of DM administered daily for 7 d, the dose-response curve of DM for induction of pulmonary ACE mirrored that for thymolysis; for both, half-maximal effects were seen at approximately 6 mug DM/d, and plateau levels at 60 mug/d. We conclude that glucocorticoids are potent inducers of ACE activity in endothelial cells in culture and in rat lung in vivo, and that the action of aldosterone and DOC reflects occupancy of glucocorticoid receptors. This effect may be of (patho)physiological relevance in regulating levels of ACE in local vascular beds, and thereby modulating local levels of the vasoactive peptides angiotensin II and bradykinin.