Author:

Keywords:

Angiotensin II, Angiotensin III, Animals, Cells, Cultured, Collagen, DNA, Dose-Response Relationship, Drug, Fibroblasts, Gels, Male, Myocardium, Peptide Fragments, Rats, Rats, Wistar, Receptors, Angiotensin, Thymidine, Science & Technology, Life Sciences & Biomedicine, Peripheral Vascular Disease, Cardiovascular System & Cardiology, angiotensin II, angiotensin III, collagen gel contraction, cardiac fibroblasts, RECEPTORS, MYOFIBROBLASTS, EXPRESSION, RATS, HYPERTENSION, ALDOSTERONE, METABOLITES, LISINOPRIL, REGULATOR, FIBROSIS, Angiotensin Receptor Antagonists, 0606 Physiology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology

Abstract:

OBJECTIVE: The aim of the present study was to investigate whether angiotensin II (Ang II), angiotensin III (Ang III) or Ang II (2-8), angiotensin IV (Ang IV) or Ang II (3-8) and Ang II (1-7), Ang II (4-8), Ang II (5-8) and Ang II (1-4) can stimulate collagen gel contraction in cardiac fibroblasts in serum-free conditions. METHODS: Cardiac fibroblasts (from male adult Wistar rats) from passage 2 were cultured to confluency and added to a hydrated collagen gel in a Dulbecco's Modified Eagle's Medium, with or without foetal bovine serum, for one, two or three days. The area of the collagen gels embedded with cardiac fibroblasts was determined by a densitometric analysis. Collagen gel contraction was characterised by a decrease in the gel area. RESULTS: Ang II dose-dependently stimulated the contraction of collagen mediated by cardiac fibroblasts after one, two or three days of incubation in a serum-free medium. Telmisartan completely blocked the Ang II-induced collagen contraction by cardiac fibroblasts. PD 123319 and des-Asp(1)-Ile(8)-Ang II had no effect on the Ang II-induced collagen contraction by cardiac fibroblasts. Ang III also stimulated the contraction of collagen mediated by cardiac fibroblasts after one, two or three days of incubation in a serum-free medium. des-Asp(1)-Ile(8)-Ang II and telmisartan completely blocked the Ang III-induced collagen gel contraction by cardiac fibroblasts. des-Asp(1)-Ile(8)-Ang II, however, had no effect on the Ang II-induced collagen gel contraction by cardiac fibroblasts. Ang IV and Ang II (4-8), (5-8), (1-7) and (1-4), however, had no effect on collagen gel contraction by cardiac fibroblasts. Addition of telmisartan, PD 123319 or des-Asp(1)-Ile(8)-Ang II alone did not affect collagen gel contraction by cardiac fibroblasts. CONCLUSION: Our data demonstrate that the effects of Ang II on the collagen gel contraction by adult rat cardiac fibroblasts in serum-free conditions are Ang II type 1(AT(1))-receptor- mediated, because they are abolished by the specific AT(1)-receptor antagonist, telmisartan, and not by the AT(2)-receptor antagonist PD 123319 or by the Ang III antagonist des-Asp(1)-Ile(8)-angiotensin. The Ang III- stimulated contraction of collagen by cardiac fibroblasts is completely blocked by the Ang III receptor antagonist, des-Asp(1)-Ile(8)-angiotensin II, and by telmisartan.