Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is dependent on vessel size.
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.
Oltman
C L
CL
Department of Veterans Affairs, University of Iowa, Iowa City, Iowa 52246, USA. coltman@blue.weeg.uiowa.edu
Kane
N L
NL
Gutterman
D D
DD
Bar
R S
RS
Dellsperger
K C
KC
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D011189:Potassium Chloride; D007334:Insulin-Like Growth Factor I; C009405:tetrabutylammonium; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases