(Hypertension. 1995;25:779-784.)
© 1995 American Heart Association, Inc.
Articles |
Insulin Attenuates Norepinephrine- Induced Venoconstriction
An Ultrasonographic Study
From the Department of Medicine, State University of New York at Buffalo, Millard Fillmore Hospitals.
Correspondence to Paresh Dandona, DPhil, Millard Fillmore Hospitals, 3 Gates Cir, Buffalo, NY 14209.
Abstract To directly assess insulin-related venomotor changes objectively and quantitatively, we used a modified ultrasonographic technique to measure venous diameter. Ten healthy men and women were studied by use of an Acuson 128 XP ultrasonograph with a linear 7.5-MHz ultrasonographic transducer (sensitivity, ±0.1 mm). Venous diameter was measured with the arm kept at 30° elevation and with a pneumatic cuff above the elbow inflated at 40 mm Hg for the last 2 minutes of each 5-minute observation period. Norepinephrine was infused at incremental concentrations of 12.5, 25, 50, and 100 ng/min (75, 150, 300, and 600 pmol/min, respectively) for 5 minutes each. Maximal venoconstriction was achieved by the dose of 100 ng/min norepinephrine, which was then combined with insulin doses of 8, 16, 24, and 32 µU/min (60, 120, 180, and 230 fmol/min, respectively) for 5 minutes each. In six different subjects, methylene blue, an inhibitor of guanylate cyclase, was infused simultaneously with 32 µU/min insulin and 100 ng/min norepinephrine. Mean resting diameter of the vein (1.8±0.6 mm [mean±SD]) increased (to 3.0±1.0 mm) after cuff inflation. Incremental doses of norepinephrine caused highly reproducible dose-dependent decreases in venous diameter (to 1.8±0.6 mm, P<.001). Incremental doses of insulin, when combined with the maximum dose of norepinephrine, caused highly reproducible dose-dependent increases in mean venous diameter (P<.001) compared with norepinephrine alone. Methylene blue, which had no independent effect on venous diameter, inhibited the venodilator effect of insulin (P<.05). Infusion of these substances caused no systemic changes in heart rate, blood pressure, or blood glucose. Modified venous ultrasonography can measure, in vivo, venomotor changes with hormones or drugs in doses that do not produce any systemic effects. Norepinephrine is a potent venoconstrictor whose local effects can be attenuated by insulin in normal subjects. Insulin-induced venodilation is blocked by methylene blue and is therefore probably cyclic guanylate monophosphate dependent.
Key Words: insulin • guanosine cyclic monophosphate • ultrasonography • norepinephrine • veins
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