Endothelial dysfunction precedes hypertension in diet-induced insulin resistance

Prasad V.G. Katakam, Michael R. Ujhelyi, Margarethe E. Hoenig, Allison Winecoff Miller

Research output: Contribution to journalArticlepeer-review


The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (~250 μM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (E(max)): 69 ± 10% of baseline] and becomes significant by day 18 (E(max): 52 ± 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 ± 1 (day 28) vs. 116 ± 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.

Original languageEnglish (US)
Pages (from-to)R788-R792
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3 44-3
StatePublished - 1998
Externally publishedYes


  • Fructose
  • Sprague-Dawley
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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