Insulin sensitivity and endothelial function in hypertension: a comparison of temocapril and candesartan.
BACKGROUND
Recent studies have suggested that angiotensin-converting enzyme inhibitors (ACEi) have a more pronounced effect on endothelial function (END) than angiotensin II receptor blocker (ARB); however, whether this pronounced effect is more beneficial to patients with insulin sensitivity (IS) remains uncertain. The present study compared the effects of ACEi and ARB on END and IS in patients with hypertension.


METHODS
A total of 23 patients with hypertension were given either ACEi or ARB alternatively in a cross-over manner for 8-week intervals. Both END and IS were examined after each treatment period; END was assessed by the response of forearm blood flow to reactive hyperemia and IS by an insulin tolerance test. The plasma levels of bradykinin (BK), NOx, tumor necrosis factor (TNF-alpha), and adiponectin (Adi) were also measured after each treatment.


RESULTS
We found that END, BK, and NOx were higher after the ACEi treatment than after the ARB treatment. Although the IS and the Adi levels were similar after both treatments, the TNF-alpha level was lower after the ARB treatment than after the ACEi.


CONCLUSIONS
We conclude that ACEi and ARB may have similar effects on insulin sensitivity, irrespective of the more pronounced effects of ACEi on endothelial function. The BK-NO pathway might contribute, at least in part, to the pronounced effect of ACEi. On the other hand, the underlying mechanisms affecting insulin sensitivity might differ for both treatments. These results suggest that endothelial function is not a major determinant of insulin sensitivity under physiologic conditions.
Tomiyama
Hirofumi
H
Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan. tomiyama@tokyo-med.ac.jp
Motobe
Kohki
K
Zaydun
Gulnisa
G
Koji
Yutaka
Y
Yambe
Minoru
M
Arai
Tomio
T
Kushiro
Toshio
T
Yamashina
Akira
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001920:Bradykinin / Q000097:blood; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D007333:Insulin Resistance; D009569:Nitric Oxide / Q000097:blood; D016037:Single-Blind Method; D013777:Tetrazoles / Q000627:therapeutic use*; D013841:Thiazepines / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D013841:Thiazepines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C055603:temocapril hydrochloride; C081643:candesartan; D001920:Bradykinin