Role of reninangiotensin system in diabetes mellitus and vascular complications

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Local formation of angiotensin II by tissue-based renin-angiotensin systems in cardiac, renal and vascular tissues represents an important pathophysiological mechanism that is upregulated in diabetes. Short-term moderate hyperglycaemia without glycosuria during the early stages of diabetes is linked with increased plasma renin activity, mean arterial pressure and renal vascular resistance (Miller etal., 1996) with activation of circulating and local renin-angiotensin systems. In animal models of diabetes, inhibition of the renin-angiotensin system with ACE inhibitor (Candido etal., 2002) or angiotensin receptor blocker (Candido etal., 2004) has been shown to prevent atherosclerosis independent of blood pressure reduction.

Improvement in insulin sensitivity follows ACE inhibition (Pollare etal., 1989; Berne etal., 1991; Donnelly, 1992; Ferrannini etal., 1994), particularly in hypertensives with type 2 diabetes (Torlone etal., 1991, 1993). Many of the initial reports were based on uncontrolled studies or flawed study design, indirect measures of insulin sensitivity or studies in patients receiving potentially confounding medications (Petrie etal., 2000). Nevertheless, data suggest that treatment of type 2 diabetes with ACE inhibition may improve glycaemic control (Heart Outcomes Prevention Evaluation (HOPE) Study Investigators, 2000) or even induce hypoglycaemia when used with insulin (Herings etal., 1995) or oral hypoglycaemic agents (Morris etal., 1997; Thamer etal., 1999).

Blockade of the renin-angiotensin system may be more effective than other antihypertensives for the same blood pressure reduction in regression of left ventricular mass (Kjeldsen etal., 2002; Okin etal., 2003). Renin-angiotensin system blockade may also reverse endothelial dysfunction in patients with coronary heart disease, hypertension and diabetes, and may favourably affect fibrinolytic balance possibly by attenuation of angiotensin II and enhancement of bradykinin (Mancini etal., 1996; Hornig etal., 1997).

More specific outcome trials in diabetes are needed to dispel the myths that seem to limit widespread use of drugs that block the renin-angiotensin system in diabetes (Lim etal., 2004). These include: fear of precipitating azotaemia with or without preexisting renal disease; fear of haemodynamic instability, particularly in patients with suspected autonomic neuropathy; fear of hyperkalaemia; and fear of precipitating renal failure due to exacerbation of bilateral renal artery stenosis, which is more common in diabetes.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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