title: Diabetic brain damage in hypertension: role of renin-angiotensin system.
abstract: Diabetes and hypertension are potent risk factors for cerebrovascular disease. We studied the effects of an angiotensin II type 1 receptor blockade (ARB) on brain damage in hypertensives in relation to diabetes. We studied cerebral metabolism (by proton magnetic resonance spectroscopy) and hemodynamics (by phase-contrast magnetic resonance angiography) before and 3 to 4 months after candesartan therapy in 20 diabetic hypertensives (DHTs) and 20 matched nondiabetic hypertensives (HTs). Silent multiple cerebral infarcts detected by brain MRI were more common in DHTs than in HTs (50% versus 25%). Cerebral N-acetyl aspartate (NAA; an indicator of functional neuronal mass) was lower in DHTs than in HTs (8.35 versus 9.58 mmol/kg; P=0.007). Baseline quantitative volume flow in the internal carotid arteries (ICAs) and the middle cerebral arteries (MCAs) was comparable between the 2 groups, whereas cerebrovascular reserve (CVR) assessed using acetazolamide (a cerebral arteriolar dilator) in ICAs (25% versus 35%; P=0.03) and MCAs (20% versus 31%; P=0.01) was lower in DHTs than in HTs. These baseline CVR and NAA values of DHT group were lower than those of 12 matched normotensives (CVR: 44% for ICA; 41% for MCA; NAA: 10.5 mmol/kg; all P<0.005). After candesartan therapy, CVR in ICAs and MCAs was significantly increased (P=0.001) independently of the reduction of the 24-hour blood pressure level, whereas the cerebral NAA level did not change. In conclusion, brain damage is advanced in DHTs. ARB partly improved the impaired cerebral microvascular function in DHTs.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical School, Tochigi, Japan. kkario@jichi.ac.jp
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.forename: Joji
authors.initials: J
authors.lastname: Ishikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hoshide
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Matsui
authors.forename: Masato
authors.initials: M
authors.lastname: Morinari
authors.forename: Kazuo
authors.initials: K
authors.lastname: Eguchi
authors.forename: Shizukiyo
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002343:Carotid Artery, Internal / Q000503:physiopathology; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000209:etiology; D048909:Diabetes Complications; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000503:physiopathology; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D001224:Aspartic Acid; C000179:N-acetylaspartate; C081643:candesartan