Cardiovascular disease renin-angiotensin system

Wang, J. G., and Staessen, J. A. (2000) Genetic polymorphisms in the renin-angiotensin system relevance for susceptibility to cardiovascular disease. Eur. J. Pharmacol. 410, 289-302. 

Danser, A. H. J., and Schunkert, H. (2000) Renin-angiotensin system gene polymorphisms potential mechanisms for their association with cardiovascular diseases. Eur. J. Pharmacol. 410,303-316. 

In view of the importance of the renin-angiotensin system in cardiovascular disease, considerable effort has been directed to developing drugs that inhibit the system. A wide variety of agents that block the formation or action of Ang II is now available. Some of these drugs block renin secretion, but the newer ones inhibit the conversion of Ang I to Ang II, block angiotensin AT receptors, or inhibit the enzymatic action of renin. 

Drugs that interfere with the renin-angiotensin system play a prominent role in the treatment of cardiovascular disease, the major cause of mortality in modem societies. 

Fonseca, V.A., Insulin resistance, diabetes, hypertension, and renin-angiotensin system inhibition reducing risk for cardiovascular disease. J Clin Hypertens (Greenwich), 2006. 8(10) p. 713-20 quiz 721-2. 

Experiments in animals have found that proliferation of vascular smooth muscle cells can be inhibited by calcitriol administration (Mitsuhashi et al. 1991). An over-active renin-angiotensin system (RAS) can impair renal function and deteriorate cardiovascular health (Li 2012), and down-regulation of RAS activity is one of the key mechanisms proposed for calcitriol (Li et al. 2002). Evidence to support this mechanism has been primarily obtained from animal experiments for example, treatment with calcitriol has been shown to down-regulate RAS and to improve cardiac function in la-hydroxylase knockout mice (Zhou et al. 2008), and in salt-sensitive rats with cardiac hypertrophy (Bae et al. 2011, Choi et al. 2011). However, a recent randomized controlled trial in patients with chronic kidney disease did not find improvements in left ventricular mass index or diastolic function by treatment with paricalcitol (active vitamin D analogue) (Thadhani et al. 2012). 

Verdecchia P, Angeli F, Mazzotta G, Gentile G, Reboldi G. The renin angiotensin system in the development of cardiovascular disease role of aliskiren in risk reduction. Vase. Health Risk Manag. 2008 4(5) 971-981. 

Bristow MR, Port JD, Kelly RA. Inhibitors of the renin-angiotensin-aldosterone system. In Braunwald E, Libby P Zipes DD, Zipes DP eds. Heart Disease A Textbook of Cardiovascular Medicine. Philadelphia WB Saunders, 2001 582-583. 

Cardiovascular Paradoxical severe hypertension occurred in three patients with advanced chronic kidney disease and bilateral renal artery stenosis. After the introduction of ramipril, an initial fall in blood pressure was followed by a paradoxical increase in blood pressure. This was postulated to be caused by activation of the renin-angiotensin-aldosterone system, as a result of renal artery stenosis and renal dysfunction [55 ]. 

Cardiovascular As was reported in SEDA-32 (p. 817), ILLUMINATE, an outcome study that recruited around 15 000 statin-eligible patients with coronary heart disease or type 2 diabetes mellitus was terminated after a median follow-up of only 550 days, because of a small but significant increase in major cardiovascular events in those taking torcetrapib - - atorvastatin compared with those taking atorvastatin alone (49 versus 35 cardiovascular deaths) [69. This occurred despite a 72% increase in HDL cholesterol and a 25% reduction in LDL cholesterol compared with the statin alone. This was almost certainly correctly attributed to activation of the renin-angiotensin-aldosterone system, resulting in increments in blood pressure and aldosterone and reduced potassium. 

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