Insulin-like growth factor I diminishes in vivo and in vitro vascular contractility: role of vascular nitric oxide.
Although most insulin-like growth factor I (IGF-I) in the circulation is generated by the liver, the hormone is also produced locally by the vasculature, suggesting its potential importance in regulation of regional blood flow. Accordingly, we studied the effects of in vivo exposure to IGF-I (5.1 nmol, i.v.) as well as in vitro incubation (100 nM) on endothelium-intact rat tail artery contractile responses to KCl and norepinephrine (NE). Systemic administration of IGF-I resulted in transient lowering of blood pressure, with maximal reduction occurring at 15 min and a return to baseline by 60 min. Maximal contractility of rings removed from animals 90 min after a bolus injection of IGF-I, when blood pressure had returned to normal, was significantly reduced for both KCl (58%) and NE (51%) without a change in sensitivity. Similar data were obtained when rings from untreated animals were preincubated in vitro for 90 min; maximal contractility in response to KCl was decreased by 31% and that to NE by 22%. L-Nitroarginine methyl ester, an inhibitor of nitric oxide (NO) production, administered in vivo before IGF-I or added to the bath buffer reversed the attenuation. The nearly identical in vivo and in vitro results suggest that the observed diminution in contractility is a direct effect of IGF-I on the vasculature, probably mediated in large part by the release of NO. This idea is supported by our observation that IGF-I stimulates NO production in intact vessels. Further, the latency required indicates that rather complex mechanisms involving actions common on both receptor- and nonreceptor-mediated events are initiated by IGF-I and/or NO.
Walsh
M F
MF
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Barazi
M
M
Pete
G
G
Muniyappa
R
R
Dunbar
J C
JC
Sowers
J R
JR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D011189:Potassium Chloride; D007334:Insulin-Like Growth Factor I; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine