Characterization of vascular reactivity in dorsal hand veins after oral rosiglitazone treatment in healthy subjects.
OBJECTIVE
In clinical studies with diabetic patients thiazolidinediones have been shown to restore abnormal vascular function which might be attributed to improved blood sugar control or to restoration of vascular endothelium and smooth muscle responsiveness. The present study was undertaken to investigate whether rosiglitazone modulates vascular responsiveness to different vasoactive agents and exerts renin-angiotensin-system (RAS)-inhibiting properties in healthy subjects in vivo.


METHODS
24 healthy male subjects were randomized to receive either rosiglitazone or placebo. Venoconstrictor responses to angiotensin II (Ang II) and phenylephrine, and endothelium-dependent response to histamine and insulin, and endothelium-independent response to glyceroltrinitrate were compared using the dorsal hand vein compliance method. Effects on the RAS were investigated by plasma level determinations of Ang II and angiotensin-(1-7). Treatment effects on the systemic arterial system were investigated by standardized pulse-wave-analysis.


RESULTS
Rosiglitazone significantly inhibited venoconstrictor responses to Ang II by 19% (-70% vs. -51% constriction, p = 0.034) and in the presence of rosiglitazone the ED80 for phenylephrine was increased (ED80: 317 A+/- 86 ng vs. 531 A+/- 102 ng; p = 0.010). Rosiglitazone treatment was without effect on endothelium-dependent dilation, blood pressure, pulse-wave-velocity and plasma angiotensin peptide levels.


CONCLUSIONS
The data of the present study in veins of healthy subjects are consistent with data from in vitro and animal studies supporting a direct effect of rosiglitazone on venous tone by modulation of the vascular smooth muscle response via AT1-receptor-downregulation.
Schindler
C
C
Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany. christoph.schindler@tu-dresden.de
Ferrario
C M
CM
Jatzke
C
C
Ahner
K
K
Brosnihan
K B
KB
Bramlage
P
P
Maywald
U
U
Oertel
R
R
Boecking
W
W
Kirch
W
W
D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D004311:Double-Blind Method; D006225:Hand / Q000098:blood supply*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D000804:Angiotensin II; D010656:Phenylephrine; D006632:Histamine; D005996:Nitroglycerin