ISH is characterized by decreased arterial compliance, usually expressed as increase in arterial stiffness. There is controversy over the mechanism of the increased stiffness. Some attribute the effect to age-related loss of distensibility in the major central arteries7 as elastic tissue is progressively replaced with collagen.8 Other investigators attribute the increased arterial stiffness to endothelial dysfunction.9 Although both factors probably contribute, the effect of endothelial dysfunction is potentially the more correctable pharmacologically.
Endothelial dysfunction is caused by free oxygen radicals in the arterial wall and by the upstream effects of reduced distal vascular flow reserve.10 Accumulation of free oxygen radicals results from age-associated cardiovascular risk factors, including atherosclerosis, diabetes mellitus, and renal impairment as well as hypertension itself.10 Endothelial dysfunction manifests clinically as impairment in acetylcholine-stimulated, endothelium-dependent, NO-mediated vasodilatation: the depressor response to antihypertensive agents which operate through endothelium-dependent mechanisms is decreased, but the response to exogenous nitrates is preserved.11
The theory that attributes arterial stiffness to endothelial dysfunction is based on the following construct of how flow is propagated in the arterial system.12 The incident pressure wave generated by ventricular systole is transmitted freely along the viscoelastic aorta until it encounters arterial branching points and the peripheral resistance offered by muscular arterioles. Here a reflected wave is generated, returning retrograde towards the heart and augmenting the oncoming forward wave. The resulting pulse wave-form depends on a balance of endogenous vasoconstrictor and vasodilator factors in the arterial tree. When there is endothelial dysfunction, NO-mediated vasodilatation in the peripheral circulation is diminished. The loss of vasodilator potential results in increased amplitude and early return of the reflected wave, causing high pulse pressure.9 These characteristics are typical of the pulse wave found using applanation tonometry in groups of elderly patients with treatment-resistant ISH.11,13 The observation that treatment with long-acting nitrates potently decreased pulse wave reflection and lowered systolic blood pressure in these patients, despite their lack of response to other antihypertensive drugs, is consistent with the presence of endothelial dysfunction.11
The ‘white coat effect’ occurs when blood pressure is increased temporarily through an autonomic neural reaction triggered by the process of measurement. This effect increases with age.14 As the systolic component often rises more than the diastolic, the type of hypertension due to a ‘white coat effect’ could be mistaken for ISH. However, a ‘white coat effect’ can be confirmed by finding a major discrepancy between automated blood pressure values (in the normal range) and observer readings (high).14
ISH is characterized by decreased arterial compliance, usually expressed as increase in arterial stiffness. There is controversy over the mechanism of the increased stiffness. Some attribute the effect to age-related loss of distensibility in the major central arteries7 as elastic tissue is progressively replaced with collagen.8 Other investigators attribute the increased arterial stiffness to endothelial dysfunction.9 Although both factors probably contribute, the effect of endothelial dysfunction is potentially the more correctable pharmacologically.Endothelial dysfunction is caused by free oxygen radicals in the arterial wall and by the upstream effects of reduced distal vascular flow reserve.10 Accumulation of free oxygen radicals results from age-associated cardiovascular risk factors, including atherosclerosis, diabetes mellitus, and renal impairment as well as hypertension itself.10 Endothelial dysfunction manifests clinically as impairment in acetylcholine-stimulated, endothelium-dependent, NO-mediated vasodilatation: the depressor response to antihypertensive agents which operate through endothelium-dependent mechanisms is decreased, but the response to exogenous nitrates is preserved.11The theory that attributes arterial stiffness to endothelial dysfunction is based on the following construct of how flow is propagated in the arterial system.12 The incident pressure wave generated by ventricular systole is transmitted freely along the viscoelastic aorta until it encounters arterial branching points and the peripheral resistance offered by muscular arterioles. Here a reflected wave is generated, returning retrograde towards the heart and augmenting the oncoming forward wave. The resulting pulse wave-form depends on a balance of endogenous vasoconstrictor and vasodilator factors in the arterial tree. When there is endothelial dysfunction, NO-mediated vasodilatation in the peripheral circulation is diminished. The loss of vasodilator potential results in increased amplitude and early return of the reflected wave, causing high pulse pressure.9 These characteristics are typical of the pulse wave found using applanation tonometry in groups of elderly patients with treatment-resistant ISH.11,13 The observation that treatment with long-acting nitrates potently decreased pulse wave reflection and lowered systolic blood pressure in these patients, despite their lack of response to other antihypertensive drugs, is consistent with the presence of endothelial dysfunction.11The ‘white coat effect’ occurs when blood pressure is increased temporarily through an autonomic neural reaction triggered by the process of measurement. This effect increases with age.14 As the systolic component often rises more than the diastolic, the type of hypertension due to a ‘white coat effect’ could be mistaken for ISH. However, a ‘white coat effect’ can be confirmed by finding a major discrepancy between automated blood pressure values (in the normal range) and observer readings (high).14
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