It is well known that cerebral blood flow is maintained constantly by autoregulation of cerebral circulation until systemic blood pressure declines to 50% of normal state. This autoregulation system is working mainly with neurogenic control. Typical models of dysautoregulation of cerebral circulation are the Shy–Drager syndrome for central autonomic nervous system disorder,1 and primary systemic amyloidosis for peripheral autonomic neuropathy.2 A patient with severe diabetic autonomic neuropathy also shows syncope at prompt standing by dysautoregulation of cerebral circulation. In stroke patients, critical dysautoregulation of cerebral circulation is observed in only a few specific conditions, except for severe acute stroke in our experience using near infrared spectroscopy with tilting bed. Long-standing hypertension without control shifts the upper limit of autoregulatory point.3 It means that the lower limit of autoregulation of cerebral circulation shifts to higher than 50% of normal mean arterial blood pressure. Concerning antihypertensive drugs, sympathetic ganglion blocker (trimetaphan, etc) or peripheral alpha-blocking agents (prazosin) may induce syncope due to orthostatic hypotension, especially in elderly people. These drugs may disturb autoregulation of cerebral circulation; therefore, lowering the blood pressure induces reduction of cerebral blood flow in early stages of the treatment. Continuous appropriate control of blood pressure may produce remodeling of the autoregulation of cerebral circulation. Kuriyama4 reported that treatment with angiotensin converting enzyme inhibitor normalized dysautoregulation of cerebral circulation in hypertensive stroke patients. Some calcium antagonists5 also showed preservation of cerebral blood flow, despite a significant reduction of blood pressure in chronic stroke patients using the Xe133 inhalation method, which is a former representative quantitative method except for positron emission tomography (PET). The PET system is the best way to measure three-dimensional cerebral blood flow and metabolism; however, it is too expensive for these clinical studies. Moriwaki et al6 reported that losartan, an angiotensin II (AT1) receptor antagonist, preserves cerebral blood flow in 16 hypertensive patients with a history of stroke (in this issue, pages 693–699). They measured cerebral blood flow before and after losartan (25–100 mg/day) treatment for 4 weeks using single photon emission tomography (SPECT) with 123I-IMP. Ambulatory blood pressure monitoring was also performed simultaneously. They calculated the absolute value of regional cerebral blood flow using the autoradiography method based on table look-up corrected by a one point arterial blood sample.7 This method is commonly used for simplified quantitative measurement of cerebral blood flow, and confirmed its usefulness in many clinical studies. They showed a significant increase of cerebral blood flow (7.7%) after treatment with losartan, despite a significant reduction in blood pressure. No significant increase of cerebellar blood flow was observed, but the difference between the change in cerebrum and cerebellum was very small. It may not have significant meaning. It is interesting that losartan reduces blood pressure more effectively, the more favorably it preserves cerebral blood flow in this study. Recently, the ACCES study (Evaluation of acute candesartan cilexetil therapy in stroke survivors)8 showed that early treatment with candesartan (angiotensin II receptor antagonist) significantly reduced mortality rate and cardiovascular event rate at 12 months after the onset in acute hypertensive stroke patients. This is the first study that confirmed the benefit of acute antihypertensive therapy in acute stroke patients. Although the mechanism of this efficacy is unknown, preservation of cerebral blood flow with lowering of blood pressure may be a possible mechanism as shown in Moriwaki's study. Moreover, the anti-inflammatory effect of angiotensin II receptor antagonist may also have some effect on the results. Clinical study for the assessment of dysautoregulation of cerebral circulation in acute stroke patients is also necessary, because it may be overestimated especially in acute stroke patients without evidence.
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