Effects on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT-1 receptor blockade.
OBJECTIVE
We have previously found improved insulin sensitivity in hypertensives after additional treatment with angiotensin II-receptor blocker (ARB) compared with calcium-channel blocker (CCB) alone, despite similar blood pressure lowering effects. In this study, we compare the effect of these two principal different vasodilating agents on the autonomic nervous system in the same patients, and test whether potential differences in these variables might explain the difference seen in insulin sensitivity.


METHODS
In a double-blind crossover study, 21 hypertensive patients were randomized to receive either 100 mg losartan (ARB) or 5 mg amlodipine (CCB) in addition to an open-labelled treatment of amlodipine 5 mg. The patients were treated for 8 weeks with either treatment regimens after a 4-week run-in and a 4-week washout period. Plasma catecholamines were measured using radioenzymatic technique and baroreflex sensitivity and heart rate variability was tested at rest and during 24-h ECG registration.


RESULTS
Plasma noradrenaline was significantly lower after additional treatment with ARB compared with CCB alone (304+/-29 pg/ml vs 373+/-43 pg/ml, p = 0.022). Heart rate variability, baroreflex sensitivity or plasma adrenaline did not differ significantly between the two treatment regimens.


CONCLUSIONS
The results may suggest that improvement of insulin sensitivity by ARB is related to decreased plasma noradrenaline and potential sympatholytic effects.
Aksnes
Tonje Amb
TA
Cardiovascular and Renal Research Center, Department of Cardiology and Department of Acute Medicine, Ullevaal University Hospital, Oslo, Norway. TonjeAmb.Aksnes@ulleval.no
Flaa
Arnljot
A
Sevre
Knut
K
Mundal
Haavard Holth
HH
Rostrup
Morten
M
Kjeldsen
Sverre Erik
SE
D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007333:Insulin Resistance; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D017311:Amlodipine; D019808:Losartan; D009638:Norepinephrine