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Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is dependent on vessel size. Am J Physiol Endocrinol Metab 2000 Jul;279(1):E176-81

Date

07/14/2000

Pubmed ID

10893337

DOI

10.1152/ajpendo.2000.279.1.E176

Scopus ID

2-s2.0-23544478975 (requires institutional sign-in at Scopus site)   50 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(2alpha). Internal diameter of coronary microvessels (resting diameter = 112.6+/-10.1 microm) was measured after endothelin constriction. Vessels were incubated in control (Krebs) solution and were treated with N(omega)-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.

Author List

Oltman CL, Kane NL, Gutterman DD, Bar RS, Dellsperger KC

Author

David Gutterman MD Emeritus Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Coronary Circulation
Coronary Vessels
Dogs
Female
Insulin
Insulin-Like Growth Factor I
Male
Microcirculation
Nitric Oxide Synthase
Potassium Channel Blockers
Potassium Channels
Potassium Chloride
Prostaglandin-Endoperoxide Synthases
Quaternary Ammonium Compounds
Vasoconstriction
Vasodilation