title: Differential vasomotor effects of insulin on gastrocnemius and soleus feed arteries in the OLETF rat model: role of endothelin-1.
abstract: The vascular actions of insulin are complex, because it can stimulate both nitric oxide-mediated dilatation and endothelin (ET)-1-mediated constriction. We examined vasoreactivity to insulin in isolated feed arteries of the gastrocnemius (GFA) and soleus muscles (SFA) of 32-week-old Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats, a hyperphagic rodent model of obesity and insulin resistance. The insulin-induced vasoreactivity of SFA and GFA was similar in LETO (healthy) and OLETF (obese/insulin-resistant) rats. However, examination of between-vessel effects revealed a number of novel insights into the heterogeneous vascular effects of insulin. Soleus feed arteries dilated more than GFA in LETO at 100 and 1000 μIU ml(-1) insulin (23 versus 6 and 28 versus 0%, respectively; P < 0.05 for between-vessel differences). Likewise, in OLETF rats there was significantly greater dilatation in SFA than GFA at 10, 100 and 1000 μIU ml(-1) insulin (28 versus 3, 30 versus 0 and 34 versus 0%, respectively; all P < 0.05). In the presence of 3 μm tezosentan, a non-specific endothelin-1 receptor blocker, insulin-induced dilatation of the GFA was enhanced such that differences between vessels were largely abolished in both groups. Furthermore, acetylecholine-induced dilatation was significantly greater in SFA than GFA within each group, whereas sodium nitroprusside-induced dilatory responses were greater in the GFA compared with the SFA. Overall, our findings indicate that the insulin/endothelin-1 vasoconstrictor pathway is more active in GFA than in SFA, independent of obesity in the OLETF rat model.
authors.affiliation: N. T. Jenkins: 115M Ramsey Center, Department of Kinesiology, University of Georgia, 330 River Road, Athens, GA 30602-6554, USA. jenkinsn@uga.edu.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Jenkins
authors.forename: Jaume
authors.initials: J
authors.lastname: Padilla
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Martin
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Crissey
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D044022:Receptor, Endothelin A / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000378:metabolism
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D007328:Insulin; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents