Systems view of the AT receptor role. This hypothetical model shows the role of the mutually antagonistic AT receptors in managing levels of inflammation. Extended expression of AT1 in the absence of sufficient expression of AT2 may lead to a failure of inflammation resolution, sustained chronic inflammation and fibrosis. This model further serves to explain the pro-inflammatory role of hypoxia and oxidative stress and their risk factors in disease. Likewise the anti-inflammatory role of IGF-1 is supported and the risk factor of decreasing circulation of IGF-1 as a result of ageing. 'External Systems' represents non-local feedback i.e. the rest of the body including hypothalamus, pituitary, thyroid, adrenal glands, liver and pancreas.