title: L-158,809 and (D-Ala(7))-angiotensin I/II (1-7) decrease PAI-1 release from human umbilical vein endothelial cells.
abstract: The endothelium is a major source of plasminogen activator inhibitor-1 (PAI-1), which plays a critical role in the regulation of fibrinolysis. There are many reports on the increase in the expression of PAI-1 by angiotensin II (Ang II). In the present study, we investigated the effects of angiotensin-related substances on the release of PAI-1 from human umbilical vein endothelial cells (HUVECs). Ang II increased PAI-1 and tissue plasminogen activator (t-PA) release, while its metabolite angiotensin-(1-7) (Ang-(1-7)) amino acid fragment decreased them. Angiotensin Type 1 (AT1) receptor antagonist, L-158,809 (L-1), and Ang-(1-7) receptor antagonist, (D-Ala(7))-angiotensin I/II (1-7) (D-Ala), decreased PAI-1 and t-PA release; angiotensin Type 2 (AT2) antagonist, PD123,319 (PD), however, did not have any effects on the release of PAI-1 and t-PA. The addition of the equal concentration or 10-times-higher concentration of L-1 to Ang II did not change PAI-1 release compared to that by Ang II. Although Ang-(1-7) and L-1 decreased PAI-1 release, there were no additional effects on the decrease of the amounts of PAI-1 by the mixture of Ang-(1-7) and the equal concentration or 10-times-higher concentration of L-1 compared to those by Ang-(1-7). The equal concentration of D-Ala to Ang II did not change the amounts of PAI-1, but the addition of the 10-times-higher concentration of D-Ala to Ang II resulted in significant decrease of the amounts of PAI-1 compared to those by Ang II. The addition of equal concentration or 10-times-higher concentration of D-Ala to Ang-(1-7) showed the significant decrease of the amounts of PAI-1 compared to those by Ang-(1-7). In conclusion, L-158,809 and (D-Ala(7))-angiotensin I/III (1-7) may be used as profibrinolytic drugs.
authors.affiliation: Department of Physiology, School of Medicine, Hamamatsu University, 1-20-1 Handa-yama, Hamamatsu, Shizuoka-ken 431-3192, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Naito
authors.forename: Tetsumei
authors.initials: T
authors.lastname: Urano
authors.forename: Akikazu
authors.initials: A
authors.lastname: Takada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takada
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005343:Fibrinolytic Agents; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: C092006:7-Ala-angiotensin (1-7); D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D007093:Imidazoles; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809; D000803:Angiotensin I; D010959:Tissue Plasminogen Activator; C118790:angiotensin I (1-7)