INSULIN-LIKE GROWTH-FACTOR-I DIMINISHES IN-VIVO AND IN-VITRO VASCULARCONTRACTILITY - ROLE OF VASCULAR NITRIC-OXIDE

Although most insulin-like growth factor I(IGF-I) in the circulation i s generated by the liver, the hormone is also produced locally by the vasculature, suggesting its potential importance in regulation of regi onal blood now. Accordingly, we studied the effects of in vivo exposur e to IGF-I (5.1 nmol, iv) as well as in vitro incubation (100 nM) on e ndothelium-intact rat tail artery contractile responses to KCl and nor epinephrine (NE). Systemic administration of IGF-I resulted in transie nt 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 bl ood pressure had returned to normal, was significantly reduced for bot h 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 decreas ed by 31% and that to NE by 22%. L-Nitroarginine methyl ester, an inhi bitor of nitric oxide (NO) production, administered in vivo before IGF -I or added to the bath buffer reversed the attenuation. The nearly id entical in vivo and in vitro results suggest that the observed diminut ion in contractility is a direct effect of IGF-I on the vasculature, p robably mediated in large part by the release of NO. This idea is supp orted by our observation that IGF-I stimulates NO production in intact vessels. Further, the latency required indicates that rather complex mechanisms involving actions common to both receptor- and nonreceptor- mediated events are initiated by IGF-I and/or NO.