Lijnen P J, Petrov V V, Jackson K C, Fagard R H
Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (Katholieke Universiteit Leuven), Belgium.
J Cardiovasc Pharmacol. 2001 Jul;38(1):39-48. doi: 10.1097/00005344-200107000-00005.
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.
分别使用特异性血管紧张素1型和2型受体拮抗剂替米沙坦和P - 186，研究了血管紧张素1型和2型受体对成年大鼠心脏成纤维细胞血管紧张素II诱导的胶原凝胶收缩的可能作用。将第2代（来自正常成年雄性大鼠）的心脏成纤维细胞培养至汇合，然后添加到水合胶原凝胶中，在含有5%胎牛血清的杜氏改良 Eagle 培养基中，分别添加或不添加血管紧张素II、血管紧张素II加替米沙坦或血管紧张素II加P - 186，培养1、2或3天。含有成年大鼠心脏成纤维细胞的对照凝胶在孵育3天后显示出显著的收缩，导致收缩至1天后面积的67.9±7.1%。血管紧张素II（10⁻⁷ M）在1、2或3天后刺激（p≤0.05）心脏成纤维细胞介导的胶原收缩。替米沙坦（10⁻⁷ M）完全阻断了血管紧张素II诱导的心脏成纤维细胞胶原收缩。P - 186（10⁻⁷ M）对血管紧张素II诱导的心脏成纤维细胞胶原收缩没有影响。单独添加替米沙坦和P - 186不影响心脏成纤维细胞的胶原凝胶收缩。我们的数据表明，血管紧张素II对成年大鼠心脏成纤维细胞胶原凝胶收缩的作用是由血管紧张素II 1型受体介导的，因为它们被特异性血管紧张素II 1型受体拮抗剂替米沙坦消除，而不是被特异性血管紧张素II 2型受体拮抗剂P - 186消除。
