Effect of telmisartan on angiotensin II-mediated collagen gel contraction by adult rat cardiac fibroblasts.
The possible contributions of the angiotensin receptor subtypes 1 and 2 on the angiotensin II-induced collagen gel contraction by adult rat cardiac fibroblasts were studied using the specific angiotensin receptor type 1 and 2 antagonists telmisartan and P-186, respectively. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and added to a hydrated collagen gel, with or without angiotensin II, angiotensin II plus telmisartan, or angiotensin II plus P-186 in Dulbecco's Modified Eagle's Medium containing 5% fetal bovine serum for 1, 2, or 3 days. Control gels containing adult rat cardiac fibroblasts showed a significant amount of contraction after 3 days of incubation, causing a contraction to 67.9 +/- 7.1% of the area after 1 day. Angiotensin II (10(-7) M) stimulated (p < or = 0.05) the contraction of collagen mediated by cardiac fibroblasts after 1, 2, or 3 days. Telmisartan (10(-7) M) completely blocked the angiotensin II-induced collagen contraction by cardiac fibroblasts. P-186 (10(-7) M) had no effect on the angiotensin II-induced collagen contraction by cardiac fibroblasts. Addition of telmisartan and P-186 alone did not affect the collagen gel contraction by cardiac fibroblasts. Our data demonstrate that the effects of angiotensin II on the collagen gel contraction by adult rat cardiac fibroblasts are angiotensin II type 1 receptor mediated because they were abolished by the specific angiotensin II type 1 receptor antagonist telmisartan but not by the specific angiotensin II type 2 receptor antagonist P-186.
Lijnen
P J
PJ
Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (Katholieke Universiteit Leuven), Belgium. paul.lijnen@med.kuleuven.ac.be
Petrov
V V
VV
Jackson
K C
KC
Fagard
R H
RH
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D024042:Collagen Type I; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077333:Telmisartan