Hemodynamic Influences of Losartan on the Brain in Hypertensive Patients

Oku, Naohiko; Kitagawa, Kazuo; Imaizumi, Masao; Takasawa, Masashi; Piao, Risyu; Kimura, Yasuyuki; Kajimoto, Kan; Matsumoto, Masayasu; Hori, Masatsugu; Hatazawa, Jun

doi:10.1291/hypres.28.43

Cited by 27 publications

(30 citation statements)

References 25 publications

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“…48 An increase in vasodilative capacity of the brain after ACE-I treatment, however, has been an equivocal finding. 49,50 Our results showed that antihypertensive treatment increased vasodilative response in the brachial artery but not in cerebrovascular vessels. The increase in endothelium-dependent vasodilation in the peripheral circulation after successful BP lowering, irrespective of type of medication, has been reported, although typically ACE-Is are superior to other medications.…”

Section: Discussionmentioning

confidence: 56%

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

et al. 2008

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Abstract-Hypertension is associated with mild decrements in cognition. In addition, regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults, who, compared with normotensive subjects, manifest greater correlation in blood flow response across task-related brain regions. Here, we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class. Treatment with lisinopril, an angiotensinconverting enzyme blocker, known to enhance vasodilative responsivity, was compared with treatment with atenolol, a ␤-blocker. Untreated hypertensive volunteers (nϭ28) were randomly assigned and treated for 1 year. Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide, a vasodilator, were assessed pretreatment and posttreatment. Peripheral brachial artery dilation during reactive hyperemia was also measured. Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection. Brachial artery flow-mediated dilation increased with treatment. No differences between medications were observed. In brain regions active in memory processing, however, regional cerebral blood flow responses were more highly correlated after treatment. Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension. This greater correlation among active brain regions, which is present as well in untreated hypertensive relative to normotensive volunteers, may represent compensation in the face of less region-specific responsivity in individuals with hypertension. M ild-to-moderate hypertension is associated with minor deficits in cognition. [1][2][3][4] Brain structure or function might account for these deficits. [5][6][7][8] Cognitive processing elicits a regional redistribution of blood flow, providing metabolic support to active neural areas. 9 Interference with this redistribution, blunting of regional blood flow, or structural loss because of poor perfusion might underlie the deficits of hypertensive individuals. Limited existing evidence supports all of these possibilities. [5][6][7][8]10 We demonstrated that, compared with normotensive individuals, those with hypertension have damped regional cerebral blood flow (CBF; rCBF) responses in parietal and thalamic areas (regions of interest [ROI]) during working memory tasks and greater correlation among rCBF responses across task-related regions. 7 Both observations might be because of a cerebrovascular adaptation to hypertension, most particularly, the remodeling of walls of small arteries, ie, thickening of the medial layer with or without a change in lumen diameter. 7 Antihypertensive medications have established influences on peripheral vascular function and may have similar effects on cerebrovascular...

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Section: Discussionmentioning

confidence: 56%

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

et al. 2008

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“…11,12 The ARB candesartan was subsequently reported to have similar effects. 13 In 2005, Oku et al 14 reported that the ARB losartan preserved CBF in hypertensive patients with a history of stroke, and effectively reduced their BP, thereby showing a successful shift in the lower limit of CBF autoregulation to a reduced BP level. These results led us to postulate that the direct blockade of angiotensin II receptors might reduce BP while maintaining an appropriate CBF in patients with impaired autoregulation.…”

Section: Introductionmentioning

confidence: 99%

Benefits of the angiotensin II receptor antagonist olmesartan in controlling hypertension and cerebral hemodynamics after stroke

et al. 2009

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The purpose of this study was to assess the relative benefits of angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) on cerebral hemodynamics and rehabilitation outcome in hypertensive stroke patients. We randomly assigned 35 patients to either the olmesartan (n¼18) or amlodipine (n¼17) treatment groups for 8 weeks. Changes in cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) were quantified using xenon-CT and rehabilitation parameters were also measured. Over 24 h, olmesartan and amlodipine both reduced blood pressure (BP) to similar levels (systolic BP, À16.1±2.7 mm Hg vs. À15.7±3.1; diastolic BP, À9.2±2.9 vs. À8.6±3.3 mm Hg, respectively). In olmesartan-treated patients, CBF significantly increased in the affected and unaffected hemispheres, and CRC increased significantly in the affected hemisphere. No increases in CBF and CRC were observed in amlodipine-treated patients. Patients treated with olmesartan showed effective rates of improvement in hand (30.0%), upper extremities (40.0%) and lower extremities (100.0%), measured by Brunnstrom stage; these improvements were significantly different from those in amlodipine-treated patients for the total (Po0.02) and lower extremity (Po0.05) scores. There were no significant differences in Barthel indices and MiniMental State Examination (MMSE) scores. Olmesartan, but not amlodipine, had beneficial effects on CBF, CRC and rehabilitation outcomes in hypertensive stroke patients, by a mechanism independent of BP reduction and possibly by normalizing CBF autoregulation. Our results suggest that olmesartan may improve cerebral circulation and rehabilitation in hypertensive stroke patients in whom CBF autoregulation is impaired.

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“…13 Antihypertensive drug-induced decreases in blood pressure reduce the risk of acquiring major cardiovascular or cerebrovascular diseases. 11,14 In addition, previous studies have reported that antihypertensive drugs, ie, ␣ 1 -and ␤ 1 -adrenoreceptor blockers, angiotensin type I receptor blockers, and angiotensin-converting enzyme inhibitors, directly influence the vasculature in both the cerebral and skeletal muscle circulations 7,[15][16][17] and suggest that antihypertensive drugs may compromise CBF regulation. However, the effect of antihypertensive drugs on autonomic neural control of the cerebral circulation remains unclear.…”

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confidence: 99%

Autonomic Neural Control of the Cerebral Vasculature

Ogoh

Eubank

Raven

2008

Stroke

158

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Background and Purpose-The effect of antihypertensive drugs on autonomic neural control of the cerebral circulation remains unclear. This study was designed to compare middle cerebral artery mean blood velocity responses to acute hypotension with and without ␣ 1 -adrenoreceptor blockade (Prazosin) in young, healthy humans. Methods-Acute hypotension was induced nonpharmacologically in 6 healthy subjects (meanϮSE; 28Ϯ2 years) by releasing bilateral thigh cuffs after 9 minutes of suprasystolic resting ischemia before and after an oral dose of Prazosin (1 mg/20 kg body weight). Results-Prazosin had no effect on thigh cuff release-induced reductions in mean arterial pressure and middle cerebral artery mean blood velocity. However, Prazosin attenuated the amount of peripheral vasoconstriction through the arterial baroreflex as evidenced by a slower return of mean arterial pressure to baseline (Pϭ0.03). Immediately after cuff release, cerebral vascular conductance index increased through cerebral autoregulation and returned to resting values as a result of an increased perfusion pressure mediated through arterial baroreflex mechanisms. The rate of regulation, an index of cerebral autoregulation, was attenuated with Prazosin (control versus Prazosin; rate of regulationϭ0.204Ϯ0.020 versus 0.006Ϯ0.053/s, Pϭ0.037). In addition, as mean arterial pressure was returning to resting values, the rate of change in cerebral vascular conductance index was decreased with Prazosin (0.005Ϯ0.006/s) compared with control (0.025Ϯ0.005/s; Pϭ0.010). Conclusions-These data suggest that during recovery from acute hypotension, decreases in cerebral vascular conductance index were mediated by increases in arterial blood pressure and sympathetically mediated cerebral vasoconstriction.

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Hemodynamic Influences of Losartan on the Brain in Hypertensive Patients

Cited by 27 publications

References 25 publications

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

Benefits of the angiotensin II receptor antagonist olmesartan in controlling hypertension and cerebral hemodynamics after stroke

Autonomic Neural Control of the Cerebral Vasculature

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