Mechanisms of impaired endothelial function associated with insulin resistance

A. W. Miller, M. E. Hoenig, M. R. Ujhelyi

Research output: Contribution to journalArticlepeer-review


Background: The insulin-resistant (IR) syndrome is causally related to hypertension and cardiovascular events; however, the underlying mechanism remains elusive. The current study was designed to determine (1) whether the IR syndrome causes vascular dysfunction and (2) whether insulin resistance alters the activity of the individual endothelium-derived relaxing factors. Methods and Results: Insulin resistance was induced in Sprague-Dawley rats by a 4-week fructose-rich diet. Subsequently, mesenteric arteries (≃250 μM) were removed from control and IR rats, and intraluminal diameter was used to assess vascular response to pharmacological probes. Studies with sodium nitroprusside showed that vascular relaxation did not differ between IR and control groups. In contrast, maximal vascular relaxation to acetylcholine (10-9 to 10-4 mol/L) in phenylephrine preconstricted arteries was decreased in the IR group (44 ± 4%) versus control (89 ± 5%) (P < .01). N- nitro-L-arginine (LNNA) pretreatment further impaired acetylcholine-induced maximal relaxation in the IR group from 44 ± 4% to 12 ± 3%; P < .01. In control rats, maximal relaxation was only slightly impaired by the addition of LNNA (89 ± 5% to 68 ± 6%; P < .05). The addition of indomethacin to acetylcholine did not affect maximal relaxation in either group. When potassium chloride (KCl) was used for preconstriction, relaxation to acetylcholine in the IR group was similar to that found with phenylephrine preconstriction (41 ± 4% v 44 ± 4%, respectively); however, KCl preconstriction significantly decreased acetylcholine-induced relaxation in control rats (89 ± 5% to 43 ± 5%; P > .01). Conclusion: Insulin resistance impairs endothelium-dependent relaxation in small mesenteric arteries. It appears that insulin resistance transforms the primary relaxant factor from endothelial-derived hyperpolarizing factor to nitric oxide. These findings suggest that hypertension and atherosclerosis associated with the IR syndrome are caused, at least in part, by endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Issue number2
StatePublished - 1998
Externally publishedYes


  • Endothelium-derived hyperpolarizing factor
  • Mesenteric arteries
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)


Dive into the research topics of 'Mechanisms of impaired endothelial function associated with insulin resistance'. Together they form a unique fingerprint.

Cite this