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To describe a logical therapy for hypertension, based on functional elements of structural changes.Structural changes to large blood vessels in hypertension include medial degenerative changes, which stiffen arteries and increase pulse wave velocity, and intimal atherosclerotic changes, which narrow arterial segments. The former cause early wave reflection with increased systolic pressure in central arteries and the left ventricle. The latter compromise blood flow to vital organs.Vasodilator drugs with arterial dilating properties are the most logical and effective therapy. These agents decrease wave reflection from peripheral sites and so reduce systolic pressure in the left ventricle and central arteries; this effect is achieved both by decreasing the stiffness of peripheral arteries and by a differential effect on arterial calibre at branching sites. Arterial vasodilators also tend to dilate stenoses and collateral vessels and thereby minimize vascular ‘steal’, whereas arterior vasodilators (such as dipyridamole, hydralazine, prazosin) have little or no significant effect on wave reflection, and so fail to reduce the ill-effects of early wave reflection on the left ventricle and central arteries. Furthermore, by dilating arterioles in normal tissue, arteriolar vasodilators can cause vascular 'steal' in the heart or brain.The most effective vasodilators are those with both arterial- and arteriolar-dilating properties. Differential effects of vasodilators on arteries and arterioles can explain some differing effects of antihypertensive agents in clinical trials, as well as differing clinical responses in individual patients.