(Hypertension. 1997;30:1128-1134.)
© 1997 American Heart Association, Inc.
Articles |
Insulin Enhances Endothelial 
2-Adrenergic Vasorelaxation by a Pertussis Toxin Mechanism
From the IRCCS "Neuromed," Pozzilli (IS) (G.L., C.V., C.M., F.M., B.T.), and the Department of Internal Medicine, School of Medicine, "Federico II" University, Naples (G.I., E.B., L.P., B.T.), Italy.
Correspondence to Bruno Trimarco, MD, Department of Internal Medicine, "Federico II" University, Via Pansini 5, 80131 Naples, Italy. E-mail trimarco{at}ds.cised.unina.it
Abstract To investigate whether insulin effect on
endothelium is related to a specific signal
transduction pathway or reflects a more generalized action of the
hormone, we studied in aortic rings of Wistar-Kyoto (WKY) rats the
effects of the hormone on endothelium-dependent
relaxations generated by acetylcholine, adenosine diphosphate,
the selective 2-adrenergic agonist UK 14,304, and the
calcium ionophore ionomycin. The responses were evaluated both in
control conditions and after 30 minutes of exposure to three different
levels of insulin (30, 100, and 500 µU/mL). Insulin failed to modify
the phenylephrine aortic contractions and the relaxations
induced by acetylcholine, adenosine diphosphate, and ionomycin.
In contrast, both 100 and 500 µU/mL insulin were able to potentiate
the UK 14,304–induced vasorelaxation (+96±19% and +91±12%,
respectively). Pertussis toxin, which causes
2-adrenergic receptor Gi uncoupling, reduced
the 2-adrenergic vasorelaxation and prevented the
insulin potentiation of the response to UK 14,304. Furthermore, in
primary cultured aortic endothelial cells from WKY, we
evaluated the conversion of [3H]arginine to
[3H]citrulline in response to acetylcholine, ionomycin,
and UK 14,304, both in control conditions and during insulin exposure.
Again, insulin did not affect basal citrulline production or
the increase induced by acetylcholine and ionomycin, whereas it
potentiated the response to UK 14,304. Finally, in aortic rings of
spontaneously hypertensive rats, insulin treatment (100 and 500
µU/mL) was unable to enhance the 2-adrenergic
vasodilator response; in vascular endothelial cells
from spontaneously hypertensive rats, insulin did not potentiate the
increase in citrulline production evoked by UK 14,304. In
conclusion, insulin selectively enhances 2-adrenergic
endothelial vasorelaxation through a pertussis
toxin–sensitive mechanism, by potentiating endothelial
nitric oxide production. This vasorelaxant mechanism is altered
in spontaneously hypertensive rats.
Key Words: aortic ring • endothelium • nitric oxide • Gi protein • insulin resistance
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