AngiotensinIIhuman (AngiotensinII) TFA 作为肾素 血管紧张素系统中关键的生物活性肽,扮演着血管收缩剂的角色并在调节人体血压中发挥中心作用。其主要通过与 G 蛋白偶联受体 (GPCRs)、血管紧张素 II 1型受体 (AT1R) 和血管紧张素 II 2型受体 (AT2R) 的相互作用来介导效应,包括刺激交感神经系统、增加醛固酮的生物合成和肾脏功能。此外,AngiotensinIIhuman TFA 促进血管平滑肌细胞的生长和 I 型及 III 型胶原在成纤维细胞中的合成,导致血管壁与心肌增厚及纤维化,并诱导细胞凋亡。还通过LOX-1依赖的氧化还原敏感路径诱导内皮细胞中的毛细血管形成。
AngiotensinII is a potent direct vasoconstrictor, causing arteries and veins to constrict, so leading to an increase in blood pressure. Angiotensin also potentiates the release of norepinephrine by a direct action on postganglionic sympathetic fibers.
4-hydroxy Valsartan is a major metabolite of the angiotensinII type 1 (AT1) receptor antagonist valsartan . It reduces platelet aggregation induced by epinephrine and collagen but not ADP in human whole blood.
Telmisartan acyl-β-D-glucuronide is a major metabolite of the angiotensinII receptor antagonist telmisartan . It does not bind human serum albumin and is cleared from rat plasma with a clearance rate of 180 ml min kg following intravenous administration.
Prostaglandin A1 (PGA1) was first isolated as a dehydration product of the PGE1 compounds found in human semen. 15-keto PGA1 is a metabolite of PGA1, produced by 15-hydroxy PG dehydrogenase. It can be produced from PGA1 in pig lung, trachea, aorta, and pulmonary artery tissue preparations. 15-keto PGA1, given at a concentration of 6 μM, causes vasoconstriction of rabbit lung that is comparable to that induced by angiotensinII.
18-Hydroxy-11-deoxy Corticosterone (18-OH-DOC) is a mineralocorticoid produced by the zona fasciculata of the adrenal gland, with its biosynthesis regulated by adrenocorticotropic hormone (ACTH) and angiotensinII. This regulation heightens 18-OH-DOC production in isolated human adrenal glomerulosa cells and allows for its formation from 11-deoxy corticosterone (DOC) in human SK-MEL188 melanoma cells. As an intermediate in progesterone metabolism, 18-OH-DOC can be converted to aldosterone in rat adrenal glands' capsular portion. Its continuous infusion (200 μg rat per day) has been shown to raise systolic blood pressure in uninephrectomized saline-drinking rats, and elevated plasma levels of 18-OH-DOC have been observed in the adb db mouse model of type 2 diabetes.