The effects of angiotensin II receptor blockers on cerebral hemodynamics in humans have not been well elucidated. The present study evaluated the effects of losartan on cerebral hemodynamics in hypertensive patients using positron emission tomography. Ten patients with essential hypertension (mean age, 60.8 years) were examined. In each patient, regional cerebral blood flow was measured by [O-15] labeled water positron emission tomography before and after the oral administration of losartan for 8 to 23 weeks. In 8 patients, the baseline regional cerebral blood flow measurement was followed by 1,000 mg of acetazolamide challenge to measure the cerebral perfusion reserve. Systemic blood pressures before and after treatment were 153.8±10.8/96.0±6.5 mmHg (systolic mean±SD/diastolic mean±SD) and 133.4±11.2/83.6±6.5 mmHg, respectively; this difference was significant. The baseline global cerebral blood flow values before and after treatment were 38.4±6.9 ml/min/100 g and 38.2±8.2 ml/min/100 g, respectively; this difference was not significant. The results of the global cerebral blood flow response to the acetazolamide challenges were not statistically different before and after treatment. A regional analysis showed no statistical difference in regional cerebral blood flow or cerebral perfusion reserve throughout the brain before and after treatment. Losartan's effect on reducing the blood pressure did not affect either the baseline regional cerebral blood flow or the cerebral perfusion reserve in patients with mild to moderate hypertension. The inclusion of losartan in anti-hypertensive regimens could be advantageous for cerebral circulation in patients with essential hypertension.
Dahlöf B, Devereux RB, Kjeldsen SE, et al, LIFE Study Group : Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995– 1003.
Vraamark T, Waldemar G, Strandgaard S, Paulson OB : Angiotensin II receptor antagonist CV-11974 and cerebral blood flow autoregulation. J Hypertens 1995; 13: 755– 761.
Strömberg C, Näveri L, Saavedra JM : Nonpeptide angiotensin AT1 and AT2 receptor ligands modulate the upper limit of cerebral blood flow autoregulation in rats. J Cereb Blood Flow Metab 1993; 13: 298– 303.
Näveri L, Strömberg C, Saavedra JM : Angiotensin II AT2 receptor stimulation increases cerebrovascular resistance during hemorrhagic hypotension in rats. Regul Pep 1994; 52: 21– 29.
VIth Joint National Committee : The sixth report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413– 2447.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA : MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. Am J Roentgenol 1987; 149: 351– 356.
Kanno I, Iida H, Miura S, et al : A system for cerebral blood flow measurement using an H215O autoradiographic method and positron emission tomography. J Cereb Blood Flow Metab 1987; 2: 143– 153.
Friston KJ, Frith CD, Liddle PF, Frackowiak RS : Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 1991; 4: 690– 699.
Matulla B, Streit G, Pieh S, et al : Effects of losartan on cerebral and ocular circulation in healthy subjects. Br J Clin Pharmacol 1997; 44: 369– 375.
Weber B, Spath N, Wyss M, et al : Quantitative cerebral blood flow measurements in the rat using a beta-probe and H215O. J Cereb Blood Flow Metab 2003; 23: 1455– 1460.
Saavedra JM, Nishimura Y : Angiotensin and cerebral blood flow. Cell Mol Neurobiol 1999; 15: 553– 573.
Brickler PE, Litt L, Banville DL, Severinghaus JW : Effects of acetazolamide on cerebral acid-base balance. J Appl Physiol 1988; 65: 422– 427.
Imaizumi M, Kitagawa K, Hashikawa K, et al : Detection of misery perfusion with split-dose 123I-iodoamphetamine single-photon emission computed tomography in patients with carotid occlusive diseases. Stroke 2002; 33: 2217– 2223.
Silvestrini M, Vernieri F, Pasqualetti P, et al : Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis. JAMA 2000; 283: 2122– 2127.
Kim JS, Moon DH, Kim GE, et al : Acetazolamide stress brain-perfusion SPECT predicts the need for carotid shunting during carotid endarterectomy. J Nucl Med 2000; 41: 1836– 1841.
Ogasawara K, Ogawa A, Yoshimoto T : Cerebrovascular reactivity to acetazolamide and outcome in patients with symptomatic internal carotid or middle cerebral artery occlusion: a xenon-133 single-photon emission computed tomography study. Stroke 2002; 33: 1857– 1862.
Inada Y, Wada T, Ojima M, et al : Protective effects of candesartan cilexetil (TCV-116) against stroke, kidney dysfunction and cardiac hypertrophy in stroke prone spontaneously hypertensive rats. Clin Exp Hypertens 1997; 19: 1079– 1099.
Pitt B, Poole-Wilson PA, Segal R, et al : Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the losartan heart failure survival study ELITE II. Lancet 2000; 355: 1582– 1587.
Dickstein K, Kjekshus J, and OPTIMAAL Steering Committee : Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002; 360: 752– 60.
Hajdu MA, Heistad DD, Baumbach GL : Effects of antihypertensive therapy on mechanism of cerebral arteriols in rats. Hypertension 1991; 17: 308– 316.
Chillon JM, Baumbach GL : Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on cerebral arteriolar dilatation in hypertensive rats. Hypertension 2001; 37: 1388– 1393.
Ito T, Yamakawa H, Bregonzio C, Terrón JA, Falcón-Neri A, Saavedra JM : Protection against ischemia and improvement of cerebral blood flow in genetically hypertensive rats by chronic pretreatment with an angiotensin II AT1 antagonist. Stroke 2002; 33: 2297– 2303.
Yang ST, Faraci FM, Heistad DD : Effects of cilazapril on cerebral vasodilatation in hypertensive rats. Hypertension 1993; 22: 150– 155.
Clozel M, Kuhn H, Hefti F : Effects of angiotensin-converting enzyme inhibitors and hydralazine on endothelial function in hypertensive rats. Hypertension 1990; 16: 532– 540.
Dohi Y, Ohashi M, Sugiyama M, Takase H, Sato K, Ueda R : Candesartan reduces oxidative stress and inflammation in patients with essential hypertension. Hypertens Res 2003; 26: 699– 704.
About this article
Cite this article
Oku, N., Kitagawa, K., Imaizumi, M. et al. Hemodynamic Influences of Losartan on the Brain in Hypertensive Patients. Hypertens Res 28, 43–49 (2005). https://doi.org/10.1291/hypres.28.43
- cerebral blood flow
- positron emission tomography
- cerebrovascular reactivity
Benefits of the angiotensin II receptor antagonist olmesartan in controlling hypertension and cerebral hemodynamics after stroke
Hypertension Research (2009)
Diastolic blood pressure influences cerebrovascular reactivity measured by means of123I-iodoamphetamine brain single photon emission computed tomography in medically treated patients with occlusive carotid or middle cerebral artery disease
Annals of Nuclear Medicine (2006)