This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ibrahim, J. Articles by Sever, P. S. Search for Related Content PubMed PubMed Citation Articles by Ibrahim, J. Articles by Sever, P. S. Related Collections ACE/Angiotension receptors Cell signalling/signal transduction Smooth muscle proliferation and differentiation Mechanism of atherosclerosis/growth factors

(Hypertension. 2000;36:917.)
© 2000 American Heart Association, Inc.

Colin Johnston - A Celebration

Action of Angiotensin II on DNA Synthesis by Human Saphenous Vein in Organ Culture

Jamila Ibrahim; Alun D. Hughes; Peter S. Sever

From Clinical Pharmacology, National Heart and Lung Institute, Imperial College School of Medicine, St Mary’s Hospital, London, UK.

Correspondence to Dr J. Ibrahim, Center for Cardiovascular Research, Kornberg Medical Research Building, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642-8679.

Angiotensin II (Ang II), an effector peptide of the renin-angiotensin system, has been reported to stimulate growth of blood vessels in vivo and smooth muscle cells in culture. In this study, the effect of Ang II on DNA synthesis was examined in deendothelialized human saphenous vein in organ culture. After 7 days’ exposure to medium containing 0.4% fetal calf serum plus Ang II, there was a marked increase in DNA synthesis. The effect of Ang II was comparable to the response to platelet-derived growth factor. Responses to Ang II were partially inhibited by the AT₁ receptor antagonist candesartan. An AT₂ receptor antagonist, PD123319, had no effect on Ang II–induced DNA synthesis, either alone or in combination with candesartan. The Ang II peptide analogues [Sar¹,Ile⁸]-Ang II (saralasin) and [Sar¹,Thr⁸]-Ang II (sarthran) acted as agonists, increasing DNA synthesis. In the presence of saralasin, responses to Ang II were inhibited. Tyrphostin-23, a tyrosine kinase inhibitor, prevented Ang II–induced DNA synthesis and reduced DNA synthesis in tissues incubated in medium containing only 0.4% fetal calf serum. In conclusion, Ang II stimulates DNA synthesis in human saphenous vein in organ culture. The effect of Ang II was more marked than has been previously reported in isolated cultured saphenous vein smooth muscle cells, and this effect is mediated in part by an angiotensin type 1 receptor. It is possible that an undefined receptor for Ang II may also be involved in the stimulation of DNA synthesis in this preparation.

Key Words: human saphenous vein • muscle, smooth • DNA synthesis • angiotensin II • organ culture • angiotensin I