Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: Blunted vasoconstriction in patients with microalbuminuria

T. G. Elliott, J. R. Cockcroft, P. H. Groop, G. C. Viberti, J. M. Ritter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

209 Citations (Scopus)

Abstract

Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to N(G)-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of N(G)-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography. Basal blood flow and vasodilator responses were similar in each group. N(G)-Monomethyl-L-arginine reduced blood flow by 41.3 ± 2.3% (mean ± SEM) in healthy control subjects, 34.0 ± 3.4% in diabetic patients without microalbuminuria and 29.2 ± 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P < 0.001). N(G)-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.

Original languageEnglish
Pages (from-to)687-693
Number of pages7
JournalClinical Science
Volume85
Issue number6
Publication statusPublished - 1993

Keywords

  • insulin-dependent diabetes mellitus
  • microalbuminuria
  • nitric oxide
  • vascular reactivity

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