Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is dependent on vessel size

Christine L. Oltman, Neal L. Kane, David D. Gutterman, Robert S. Bar, Kevin C. Dellsperger

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Insulin and insulin-like growth factor I (IGF-I) influence numerous metabolic and mitogenic processes; these hormones also have vasoactive properties. This study examined mechanisms involved in insulin- and IGF-I-induced dilation in canine conduit and microvascular coronary segments. Tension of coronary artery segments was measured after constriction with PGF(2α). Internal diameter of coronary microvessels (resting diameter = 112.6 ± 10.1 μm) was measured after endothelin constriction. Vessels were incubated in control (Krebs) solution and were treated with N(w)-nitro-L-arginine (L-NA), indomethacin, or K+ channel inhibitors. After constriction, cumulative doses of insulin or IGF-I (0.1-100 ng/ml) were administered. In conduit arteries, insulin produced modest maximal relaxation (32 ± 5%) compared with IGF-I (66 ± 12%). Vasodilation was attenuated by nitric oxide synthase (NOS) and cyclooxygenase inhibition and was blocked with KCl constriction. Coronary microvascular relaxation to insulin and IGF-I was not altered by L-NA, indomethacin, tetraethylammonium chloride, glibenclamide, charybdotoxin, and apamin; however, tetrabutylammonium chloride attenuated the response. In conclusion, insulin and IGF-I cause vasodilation in canine coronary conduit arteries and microvessels. In conduit vessels, NOS/cyclooxygenase pathways are involved in the vasodilation. In microvessels, relaxation to insulin and IGF-I is not mediated by NOS/cyclooxygenase pathways but rather through K+-dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)E176-E181
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume279
Issue number1 42-1
DOIs
StatePublished - Jul 1 2000
Externally publishedYes

Keywords

  • Coronary circulation
  • Coronary microcirculation
  • Diabetes mellitus
  • Dogs
  • Potassium channels

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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