Endothelin-induced venoconstriction is unaffected by type 2-diabetes: in vivo effect of histamine on the endothelin action on veins.
In vitro studies indicate that the intact endothelium prevents the access of circulating endothelin to vascular smooth muscle cells. Disease states like diabetes, that are associated with endothelium dysfunction, might facilitate the access of endothelin to vascular smooth muscle, causing increased vasoconstriction. To investigate whether differences between diabetic and nondiabetic subjects could be detected on superficial veins, venous diameter changes in response to local infusions of endothelin (1.53, 3.11 and 6.22 pmol/min) were compared in type 2-diabetics with albuminuria (greater than 300 mg/day) and borderline hypertension (diastolic blood pressure 90-95 mmHg), and in healthy volunteers. In addition, we studied the effect of histamine on the endothelin-induced venoconstriction. The dorsal hand vein compliance technique was employed. Endothelin caused a dose-dependent, slow-onset constriction of the hand vein in all subjects, without any difference in endothelin responsiveness between diabetic and control subjects. The maximal venoconstriction at 6.22 pmol endothelin/min was 29 +/- 26% (% of venous diameter at base line) in diabetics and 23 +/- 22% in controls (p greater than 0.02). Co-infusion of endothelin and a dose of histamine with minimal venodilatory effect ("ED5-ED20") had no influence on the endothelin responsiveness of the hand veins, in that the maximal venoconstriction after 6.22 pmol endothelin/min was 25 +/- 23% without, and 23 +/- 16% with added histamine. Submaximally venodilating histamine doses ("ED60-ED90") markedly attenuated the endothelin-induced venoconstriction (maximal venoconstriction: 63 +/- 43%). These data, obtained in veins, argue against a generalized defect in vascular responsiveness to endothelin associated with diabetes.
Blöchl-Daum
B
B
Department of Medicine III, Vienna University Hospital, Austria.
Vierhapper
H
H
Eichler
H G
HG
Waldhäusl
W
W
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006225:Hand / Q000098:blood supply; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
D016232:Endothelins; D006632:Histamine