<qa>  What is the effect of aldosterone receptor blockade with spiron4. Is the effect of aldosterone receptor blockade with spironolactone mediated by lowering arterial pressure? Spironolactone is now recognised as an effective anti-hypertensive agent for patients with hypertension, even when this is resistant to other drugs. It is therefore necessary to consider whether any improvements that do occur in measures such as arterial stiffness and LV mass after spironolactone might simply be due to this effect. Several lines of evidence suggest that the effects of aldosterone inhibition are independent of blood pressure. The work of Rocha et al. in experimental animals clearly showed that inhibition of myocardial and aortic fibrosis, nephrosclerotic and cerebrovascular lesions by aldosterone inhibition occurred in the absence of changes in blood pressure. In humans, in the RALES and EPHESUS studies, the mortality effects occurred in the absence of any fall in blood pressure. In patients with controlled hypertension and diabetic nephropathy, a group relevant to the work proposed in this application, high dose spironolactone treatment 100 mg per day did not result in a fall in either systolic or diastolic blood pressure but did reduce albuminuria independently of blood pressure. Finally, Professor Struthers, a national authority on aldosterone and the cardiovascular system, has shown that in trials of spironolactone in severe heart failure and diabetes, no fall in blood pressure occurred with spironolactone suggesting that the beneficial action of spironolactone on endothelial function was not mediated by such an effect. personal communication. Nevertheless, an effect mediated by a reduction in blood pressure cannot be excluded. In order to examine this hypothesis, we will examine the relationship between the magnitude of changes in end points and changes in blood pressure. 