Selective reduction of cPP Sample Clauses

Selective reduction of cPP. Vasodilators are the most widely used treatment for hypertension and heart failure. In hypertension they have been shown to improve cardiovascular outcome due to their blood pressure lowering effects, although specific class effects beyond blood pressure lowering could also be implicated.102 Their common feature is their effect to reduce peripheral resistance103-107, once thought to be the sole haemodynamic culprit leading to hypertension. For the last two decades it has been increasingly recognised that brachial DBP control is often achievable but not SBP and PP, even under clinical trial conditions.3, 8, 108 Often multiple drugs are required to optimise SBP control4, 109 and in an attempt to optimise SBP, further resistance arteriolar vasodilatation precipitates a greater than desired fall in DBP thus potentially compromising perfusion pressure to vital organs. This is especially true in the context of ISH, the commonest type of hypertension in middle aged and elderly patients.42 Beside reduction in peripheral resistance, therefore, the rationale for design of new vasodilators specifically targeting PP reduction should be the ability to manipulate arterial stiffness and/or pressure wave reflection within the cardiovascular system. Aortic stiffness Left ventricular contraction and relaxation Vascular tone in muscular conduit arteries Vascular tone in resistance arterioles Figure 4: Schematic diagram showing the potential haemodynamic targets for optimisation of ventricular vascular coupling and pulse pressure reduction. Figure 4 shows the various components within the cardiovascular system that could potentially influence cPP. These include aortic stiffness, muscular arterial tone influencing pressure wave reflection and ventricular contraction and relaxation. Aortic Stiffness Arterial stiffening is an ageing process driven by a complex interaction between systemic factors and local haemodynamic forces that activate mechanical and cellular changes within the arterial wall.18, 110, 111 Large elastic arteries are arbitrary defined as arteries with internal diameter above 2mm and muscular large arteries with internal diameter between 150μm – 2mm.22 The structural integrity of the arterial wall, which is a balance of elasticity and tensile strength is determined by the proportion of elastin to collagen in the extracellular matrix and the number of vascular smooth muscle cells (VSMC).110, 111 From the aortic root down to the distal 5cm of thoracic aorta, elast...