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Angiotensin II-induced stimulation of collagen secretion and production in cardiac fibroblasts is mediated via angiotensin II subtype 1 receptors

Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (KU Leuven), Belgium, paul.lijnen@ med.kuleuven.ac.be

Victor V Petrov

Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (KU Leuven), Belgium

Robert H Fagard

Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (KU Leuven), Belgium

The possible contributions of the angiotensin receptor subtypes 1 (AT₁) and 2 (AT₂) to angiotensin II (Ang II)-induced changes in collagen secretion and production were studied using the specific angiotensin AT₁- and AT ₂-receptor antagonists telmisartan and P-186, respectively. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated in the presence of 10^-10 to 10^-6 M Ang II in serum-free Dulbecco's MEM medium for 24 hours. Collagen production and secretion were assayed by ³H-Proline incorporation; non-collagen production and secretion were also calculated. Ang II dose-dependently increased collagen secretion and production in rat adult cardiac fibroblasts in culture. Non-collagen secretion and production were also concentration-dependently increased by Ang II. Addition of 100 nmol/l Ang II increased (p<0.01) collagen secretion and production by 75±6 (SEM)% and 113±23%, respectively, and non-collagen secretion and production by 65±6% and 57±16%, respectively. Pretreatment of cardiac fibroblasts with telmisartan completely blocked the Ang II-induced increase in collagen secretion (p<0.001) and production (p<0.05) and in non-collagen secretion (p<0.01) and production (p<0.01). P-186 had no effect on the Ang II-induced increase in collagen secretion and production. Addition of telmisartan and P-186 did not affect collagen secretion and production in basal cardiac fibroblasts. Our data demonstrate that the effects of Ang II on collagen secretion and production in adult rat cardiac fibroblasts in culture are AT₁-receptor mediated, since they were abolished by the specific AT₁-receptor antagonist, telmisartan, but not by the specific AT₂-receptor antagonist, P-186.

Key Words: collagen • angiotensin II • telmisartan • cardiac fibroblasts

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 2, 117-122 (2001)
DOI: 10.3317/jraas.2001.012


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