Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression.

Abstract

Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward Invest. 1994Invest. . 93:2372Invest. -2378

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

“…33 Cultures of adult rat cardiac fibroblasts express AT 1 but not AT 2 receptors and angiotensin II-stimulated increase in [Ca ++ ] i and several growth-related metabolic events including c-fos gene expression and increased synthesis of DNA, RNA and protein and collagen type I synthesis were blocked by losartan. 34 In the experiments using cultured rat or human mesangial cells, losartan inhibited the angiotensin II-stimulated hypertrophy [35][36][37] and proliferation 36,37 of the mesangial cells. Similar results have been reported in the experiments using cultured vascular smooth muscle cells; namely, angiotensin II with or without PDGF or EGF stimulated the proliferation of cultured smooth muscle cells, which was inhibited by losartan [38][39][40] or candesartan.…”

The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias

“…26 Traditionally, the effect of RAAS on promoting atrial and ventricular arrhythmias is explained based on increased cardiac hypertrophy, fibrosis, and heterogeneity of the cardiac tissue. 27 Nevertheless, such a model fails to explain the observed reversal of the proarrhythmic effects upon treatment with ACEIs or ARBs, suggesting other electrophysiological effects of RAAS activation. RAAS has manifold effects on the cardiovascular system and various possible pathways have been proposed as the link underlying the relationship between RAAS and arrhythmias.…”

Myocardial fibrosis in response to Angiotensin II is preceded by the recruitment of mesenchymal progenitor cells

“…Cardiac fibroblasts are activated in response to hypertrophic stimuli, including AngII. [14][15][16][17] Furthermore, fibroblasts proliferate and increase the production of ECM proteins in response to AngII exposure in vitro. However, the in vivo data available to support this response to AngII is limited.…”

“…However, the in vivo data available to support this response to AngII is limited. 1,[14][15][16][17] Finally, if myofibroblasts make up a component of the cells that accumulate in the myocardium after AngII exposure, their origin remains to be determined. Myofibroblasts can arise from the activation and proliferation of resident fibroblasts or from several different sources including endothelial-mesenchymal transitions and blood borne mesenchymal progenitor cells (referred to as fibrocytes).…”