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**4** 

*Italy* 

**Potassium-Sparing Diuretics in Hypertension** 

*Clinica Medica, Department of Experimental and Clinical Medicine, University of Udine,* 

ENaC: amiloride-sensitive epithelial sodium channel; ROMK: renal outer medullary K channel; BK K+: flow-sensitive maxi K channel; AQP-2: apical aquaporin; AQP-3 and 4: basolateral aquaporin; 11β-HSD2: 11β-hydroxysteroid dehydrogenase; NAD: nicotinamide adenine dinucleotide; ROS: reactive oxygen species; CYP11B2: aldosterone synthase; GPR30: G protein coupled receptor; PI3K: phosphatidylinositol 3-kinase; ERK: extracellular signalregulated kinase; NYHA: New York Heart Association; HFPSF: heart failure and preserved systolic function (HFPSF); ACE: angiotensin-converting enzyme; CCB: calcium-channel

Many clinical studies have reported that cardiovascular morbidity and mortality have a continuous relationship with both systolic and diastolic blood pressures. Although some of these studies have reported that this relationship is steeper for stroke, in some European countries the attributable risk, that is the excess of events due to increased blood pressure, appears to be greater for coronary artery disease (Prospective Studies Collaboration, 2002). Current evidence indicates that both systolic and diastolic blood pressure levels have a continuous and independent relationship with a variety of additional organ complications, including congestive heart failure, renal failure, and peripheral artery disease. The wide prevalence of hypertension in the general population (Wolf-Maier et al. 2003) explains why hypertension has been identified as the first cause of death worldwide by the World Health Organization. This is also why today hypertension is considered as the most important

Recent guidelines have put strong emphasis on the relevance of hypertension-related subclinical organ damage and have prescribed that signs of organ involvement should be sought with great care. In fact, a large body of evidence indicates that hypertensive subclinical organ damage, including left ventricular hypertrophy, microalbuminuria, and thickening of inner vascular layers, is critical in determining the cardiovascular risk of individuals with high blood pressure (The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and of the European Society of Cardiology, 2007). In patients with high blood pressure, left ventricular hypertrophy has been shown repeatedly to be associated with an increased incidence of cardiovascular events, and similar evidence has been obtained for carotid intima-media thickening and microalbuminuria. Also and most important, prospective studies have demonstrated that reduction in left ventricular mass, intima-media thickness, and urinary protein excretion

**1. Introduction** 

blockers.

Abbreviations and acronyms in this chapter.

correctable risk factor for cardiovascular diseases.

Cristiana Catena, GianLuca Colussi and Leonardo A. Sechi

