Endothelial renin-angiotensin pathway. Adrenergic regulation of angiotensin secretion.
Cultured bovine aortic endothelial cells (BAECs) express the complete renin-angiotensin system and secrete angiotensins. In this study, we examined the adrenergic influence on the secretion of angiotensins from BAECs. Angiotensins were determined by high-performance liquid chromatography and radioimmunoassay. At basal state, BAECs contain angiotensin I, angiotensin II, and angiotensin III at concentrations of 2.5 +/- 1.3, 4.8 +/- 2.3, and 3.4 +/- 1.5 pg/10(6) cells, respectively. Angiotensin I, angiotensin II, and angiotensin III concentrations in the culture medium were 8.3 +/- 4.4, 9.4 +/- 3.5, and 9.9 +/- 3.3 pg/10(6) cells, respectively. Isoproterenol (0.1-10 microM) increases secretion of angiotensins I, II, and III in a dose-dependent manner. Increase in angiotensin secretion induced by isoproterenol (10 microM) can be inhibited by beta 2-adrenoceptor antagonist ICI 118,551 (1 microM), but not by beta 1-adrenoceptor antagonist atenolol (1 microM). Forskolin (1-1,000 microM) mimics the isoproterenol-induced response. In contrast, alpha-adrenergic agonist phenylephrine (1-100 microM) inhibits the secretion. Pretreatment of BAECs with captopril (1 microM) inhibits the accumulation of angiotensin II and angiotensin III in the culture medium, but not angiotensin I. These findings suggest that BAEC production and/or secretion of angiotensins is regulated by adrenergic mechanisms.
Tang
S S
SS
Division of Vascular Medicine and Atherosclerosis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Stevenson
L
L
Dzau
V J
VJ
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000805:Angiotensin III / Q000378:metabolism; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D004730:Endothelium, Vascular / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*
D003470:Culture Media; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D000805:Angiotensin III; D010656:Phenylephrine; C026777:ICI 118551; D001262:Atenolol; D000803:Angiotensin I; D002216:Captopril; D007545:Isoproterenol