Effect of urotensin II on skin microvessel tone in diabetic patients without heart failure or essential hypertension.
Urotensin II (UII) is a potent vasoconstrictor peptide. Increased plasma levels and kidney expression of UII and its receptor have been observed in diabetes mellitus (DM). The aim of the present study was to evaluate the direct effect of exogenous UII on microvascular tone in DM patients compared with healthy controls. Vasoactive effect of UII (10(-12), 10(-9) and 10(-7) mol/L) on skin microvascular tone was evaluated in 12 controls and 12 DM patients (Type 1 or Type 2) without concomitant heart failure or essential hypertension using the non-invasive technique of iontophoresis and laser Doppler velocimetry. In addition, responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were evaluated. Urotensin II dose-dependently dilated skin microvasculature in control subjects (-51.8 +/- 59.4, 138.6 +/- 101.5, 204.2 +/- 115.7 and 207.5 +/- 81.6 arbitrary flux units (AFUs) for MilliQ and 10(-12), 10(-9) and 10(-7) mol/L UII, respectively) and dose-dependently vasoconstricted the microvasculature in DM patients (100.8 +/- 81.2, 46.2 +/- 85.1, 35.4 +/- 81.4 and 26.6 +/- 79.6 AFUs for MilliQ and 10(-12), 10(-9) and 10(-7) mol/L UII, respectively). Blood flow in control subjects and DM patients was differed significantly, with pair-wise comparisons indicating differences for 10(-9) and 10(-7) mol/L UII (P = 0.04 and P = 0.003). Results of blood flow in diet-controlled DM patients (204.7 +/- 193.6, 261.2 +/- 212.8, 256.1 +/- 202.9 and 233.7 +/- 115.9 AFUs for MilliQ and 10(-12), 10(-9) and 10(-7) mol/L UII, respectively) were similar to those in control subjects compared with results for DM patients receiving antidiabetic medication (48.8 + 80.0, -61.4 +/- 49.1, -75.0 +/- 40.0, -91.7 +/- 80.0 AFUs for MilliQ and 10(-12), 10(-9) and 10(-7) mol/L UII, respectively). Between-group significance remained after adjustment for baseline blood pressure values. Acetylcholine vasodilator responses were attenuated in DM patients compared with those in control subjects (1309.5 +/- 488.6 vs 3498.0 +/- 912.5 AFUs, respectively), whereas SNP responses were similar in the two groups (1467.9 +/- 411.3 vs 1984.4 +/- 410.7 AFUs, respectively). In conclusion, UII causes net vasoconstriction in DM. The UII-induced increases in peripheral vascular tone may contribute to DM-related cardiovascular complications.
Zomer
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NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventative Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia.
de Ridder
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I
Kompa
A
A
Komesaroff
P
P
Gilbert
Re
R
Krum
H
H
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007478:Iontophoresis / Q000379:methods; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply*; D014579:Urotensins / Q000008:administration & dosage* / Q000009:adverse effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation
D014579:Urotensins; C029677:urotensin II