Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors.
We aimed to compare the effects of two different vasodilating principles, angiotensin II-receptor blockade and calcium channel blockade, on peripheral insulin-mediated glucose uptake in patients with hypertension and other cardiovascular risk factors. Twenty-one hypertensive patients (11 women and 10 men) with mean age 58.6 years (range 46-75 years), body mass index 29.2 +/- 1.0 kg/m(2) and blood pressure 160 +/- 3/96 +/- 2 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg. After 8 weeks of treatment, all patients underwent clinical examination and laboratory testing, and 17 of them underwent a hyperinsulinaemic isoglycaemic glucose clamp. After a 4-week open-label wash-out phase, the participants crossed over to the opposite treatment regimen and final examinations with hyperinsulinaemic isoglycaemic glucose clamp after another 8 weeks. Blood pressure was lowered to the same level in both treatment periods. The glucose disposal rate was significantly higher after treatment with losartan 100 mg + amlodipine 5 mg compared to amlodipine 10 mg (4.9 +/- 0.4 vs 4.2 +/- 0.5 mg/kg/min, P = 0.039). Thus our data suggest that angiotensin II-receptor blockade with losartan improves glucose metabolism at the cellular level beyond what can be expected by the vasodilatation and blood pressure reduction alone.
Aksnes
T A
TA
Department of Cardiology, Ullevaal University Hospital, Oslo, Norway. TonjeAmb.Aksnes@ulleval.no
Reims
H M
HM
Guptha
S
S
Moan
A
A
Os
I
I
Kjeldsen
S E
SE
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D007328:Insulin; D008055:Lipids; D017311:Amlodipine; D014527:Uric Acid; D019808:Losartan