Metabolism - Clinical and Experimental
Volume 47, Issue 9 , Pages 1037-1039, September 1998

Insulin-induced vasodilation is dependent on tetrahydrobiopterin synthesis☆

  • Subodh Verma

      Affiliations

    • Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
    • Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada
    • Current address for S.V.: Division of Cardiology, Foothills Hospital, Calgary, Canada.
    • ,
  • Emi Arikawa

      Affiliations

    • Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
    • Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada
    • ,
  • Linfu Yao

      Affiliations

    • Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
    • Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada
    • ,
  • Ismail Laher

      Affiliations

    • Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
    • Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada
    • ,
  • John H. McNeill

      Affiliations

    • Corresponding Author InformationAddress reprint requests to John H. McNeill, PhD, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
    • Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
    • Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada

Received 1 August 1997; accepted 23 March 1998.

Abstract 

Insulin has been shown to elicit vasodilation through increases in nitric oxide (NO) production. To examine whether insulin may modulate the availability of tetrahydrobiopterin (BH4) (an absolute cofactor requirement for NO synthase activation), we studied the effects of insulin (150 nmol/L) on femoral arterial reactivity (to norepinephrine [NE]) in the presence and absence of 2,4-diamino-6-hydroxypyrimidine (DAHP), a specific inhibitor of BH4 production. Our data indicate that inhibition of BH4 synthesis results in an attenuation in the vasodepressor effect of insulin. One possibility is that insulin may regulate NO production by increasing cofactor (BH4) availability for activation of NO synthase.

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☆ Supported by a grant from the Heart and Stroke Foundation of British Columbia and Yukon. S.V. is a Fellow of Medical Research Council of Canada. E.A. is a recipient of a University of British Columbia Graduate Fellowship and a Heart and Stroke Foundation of BC & Yukon Summer Studentship Award.

PII: S0026-0495(98)90273-6

Metabolism - Clinical and Experimental
Volume 47, Issue 9 , Pages 1037-1039, September 1998

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