Diabetic brain damage in hypertension: role of renin-angiotensin system.
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.
Kario
Kazuomi
K
Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical School, Tochigi, Japan. kkario@jichi.ac.jp
Ishikawa
Joji
J
Hoshide
Satoshi
S
Matsui
Yoshio
Y
Morinari
Masato
M
Eguchi
Kazuo
K
Ishikawa
Shizukiyo
S
Shimada
Kazuyuki
K
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
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D001224:Aspartic Acid; C000179:N-acetylaspartate; C081643:candesartan