Insulin-induced arteriolar dilation after tyrosine kinase and nitric oxide synthase inhibition in hamster cheek pouch microcirculation.
We investigated the effects of tyrosine kinase (TK) and nitric oxide synthase (NOS) inhibition on insulin-induced dilation of arterioles. We determined the arteriolar diameter, red blood cell velocity (VRBC) and blood flow changes in hamster cheek pouch microcirculation as affected by insulin in presence of TK and NOS inhibitors, genistein, piceatannol and NG-monomethyl-L-arginine (L-NMMA). Microvessels were visualized by a fluorescent microscopy technique. Arteriolar diameter and VRBC were measured after topical application of insulin and genistein or piceatannol or L-NMMA. Insulin (10 microU/ml) induced diameter and VRBC increase in A3 and A2 arterioles by 30 +/- 5 and 123 +/- 4%, 16 +/- 4 and 102 +/- 3%, as percent of baseline values, respectively. After genistein or piceatannol prior to insulin A3 and A2 arterioles dilated by 10 +/- 4, 5 +/- 2% and 9 +/- 4, 2 +/- 1%, respectively. After L-NMMA prior to insulin A2 and A3, arteriole diameters increased by 12 +/- 3 and 7 +/- 2%, respectively. VRBC increased significantly in all the cases. TK and NOS inhibitors applied together abolished insulin-induced dilation with a reduction in VRBC and blood flow. In conclusion, full insulin-induced dilation of hamster cheek pouch arterioles requires TK signaling pathways. Furthermore, activation of insulin receptors, as well as other TK receptors, appears to be required for vasomotor tone regulation.
CNR Institute of Clinical Physiology, University of Pisa, Italy. sibert@nsifc.ifc.pi.cnr.it
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Bertuglia
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Colantuoni
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002610:Cheek / Q000098:blood supply*; D006224:Cricetinae; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013267:Stilbenes / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007328:Insulin; D013267:Stilbenes; D019323:omega-N-Methylarginine; C041525:3,3',4,5'-tetrahydroxystilbene; D019833:Genistein; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011505:Protein-Tyrosine Kinases