Angiotensin-(1-9), the product of angiotensin I conversion in platelets, enhances arterial thrombosis in rats.
Angiotensin (Ang) (1-9) is the renin-angiotensin-system peptide found in the plasma of healthy volunteers and after angiotensin-converting-enzyme inhibitors therapy. In vitro experiments proved that Ang-(1-9) may be produced from Ang I. In our study, we tried to expand the poor data about the in vivo properties of Ang-(1-9). We revealed that Ang-(1-9) enhanced electrically stimulated arterial thrombosis in the carotid artery of Wistar rats. Losartan, a selective blocker of AT1 receptor for Ang II, abolished the prothrombotic activity of Ang-(1-9). This peptide increased plasma level of fibrinogen, augments fibrin generation, and similarly to Ang II, potentiated collagen induced platelet aggregation. Using HPLC, we found that after incubation of Ang-(1-9) with platelet homogenates or after intravenous administration this peptide is converted to Ang II. We concluded that Ang-(1-9) exerts an Ang II-like prothrombotic effect due to the conversion to Ang II in the circulatory system of rats and that platelets are involved in this process.
Kramkowski
K
K
Department of Pharmacodynamics, Medical University in Bialystok, Poland.
Mogielnicki
A
A
Leszczynska
A
A
Buczko
W
W
D000803:Angiotensin I / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D010446:Peptide Fragments; C506331:angiotensin I (1-9); D000804:Angiotensin II; D000803:Angiotensin I; D019808:Losartan