Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients.
OBJECTIVE
Disturbed endothelial function is closely associated with hyperinsulinaemia and insulin resistance in essential hypertension. The aims of this study were: 1) to evaluate whether the two alternative drugs, angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (Ang II) antagonists, had comparable effects on glucose metabolism and endothelial function. 2) to determine whether they improve endothelial dysfunction through modulating insulin resistance and oxidative stress.


METHODS
Essential hypertensive patients were randomised into two groups: Twelve (nine patients in final analysis) patients were given enalapril (enalapril group), and twelve (nine patients in final analysis) were given losartan (losartan group). Twelve sex- and age-matched normotensive volunteers were included as controls. Before and after six months of treatment, endothelial function, insulin sensitivity and lipid peroxidation (TBARs) and NO metabolites (NOx) were evaluated.


RESULTS
Endothelial function, measured as flow mediated dilatation (FMD), was improved in both of the treatment groups (p=0.0001). Calculated insulin sensitivity index also improved in the enalapril-treated group (p=0.05) but not in the losartan-treated group, compared with baseline levels. TBARS values decreased significantly in the enalapril group compared with baseline levels (p<0.001). FMD was positively correlated with insulin sensitivity index (r=0.32, p<0.05) and NOx levels (r=0.39, p=0.01) and negatively correlated with TBARS levels (r=-0.53, p=0.0002) in hypertensive patients.


CONCLUSIONS
Inhibition of the renin-angiotensin system, either with ACE inhibitors or AT(1)-receptor blockers improves endothelial dysfunction. ACE inhibition has prominent effects on improving insulin sensitivity and decreasing oxidative stress in essential hypertensive patients.
Yavuz
Dilek
D
Section of Endocrinology and Metabolism, Marmara University, Istanbul, 34660, Turkey.
Koç
Mehmet
M
Toprak
Ahmet
A
Akpinar
Ihsan
I
Velioğlu
Ayliz
A
Deyneli
Oguzhan
O
Haklar
Goncagül
G
Akalin
Sema
S
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D004656:Enalapril; D019808:Losartan