Mechanisms initiating integrin-stimulated flow recruitment in arteriolar networks.
Our purpose was to investigate the local mechanisms involved in network-wide flow and diameter changes observed with localized downstream vitronectin receptor ligation; we tested specific K or Cl channels known to be involved in either dilation or elevated permeability following vitronectin receptor activation and tested integrin-linked pathway elements of tyrosine phosphorylation and protein kinase C (PKC). Arteriolar networks were observed in the cheek pouch tissue of anesthetized (pentobarbital sodium, 70 mg/kg) hamsters (n=86) using intravital microscopy. Terminal arteriolar branches of the networks were stimulated with micropipette LM609 (0.5-10 microg/ml, 60 s) alone or with inhibitors (separate micropipette). Hemodynamic changes (diameter, red blood cell flux, velocity) were observed at the upstream entrance to the network. LM609 alone stimulated first an increase in wall shear stress (WSS), followed by a dilation that recovered WSS to baseline or below. K channel inhibition (glybenclamide, 4-AP) had no effect on the initial peak in WSS, but decreased remote vasodilation. Cl channel inhibition (DIDS, IAA-94, niflumic acid) or inhibition of PKC (chelerythrine) prevented the initial peak in WSS and decreased remote vasodilation. Inhibition of tyrosine phosphorylation (genistein) prevented both. With the use of nitro-arginine at the observation site, the initial peak in WSS was not affected, but remote vasodilation was decreased. We conclude the remote response consists of an initial peak in WSS that relies on both PKC activity and depolarization downstream, leading to an upstream flow mediated dilation and a secondary remote dilation that relies on hyperpolarization downstream at the stimulus site; both components require tyrosine phosphorylation downstream.
Frame
Mary D
MD
Department of Biomedical Engineering, Stony Brook University, HSC T18-030, Stony Brook, NY 11794-8181, USA. mframe@notes.cc.sunysb.edu
Rivers
Richard J
RJ
Altland
Owen
O
Cameron
Scott
S
D000818:Animals; D001160:Arterioles / Q000502:physiology*; D001783:Blood Flow Velocity / Q000502:physiology*; D006224:Cricetinae; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D039302:Integrin alphaVbeta3; D011493:Protein Kinase C