Mechanisms initiating integrin-stimulated flow recruitment in arteriolar networks

Mary D. Frame, Richard Rivers, Owen Altland, Scott Cameron

Research output: Contribution to journalArticle

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)2279-2287
Number of pages9
JournalJournal of Applied Physiology
Volume102
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Integrins
Dilatation
Integrin alphaVbeta3
Vasodilation
Protein Kinase C
Phosphorylation
Tyrosine
Niflumic Acid
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Genistein
Cheek
Glyburide
Pentobarbital
Cricetinae
Protein-Tyrosine Kinases
Ligation
Arginine
Permeability
Erythrocytes
Hemodynamics

Keywords

  • Flow-dependent dilation
  • Remote responses
  • Vascular communication

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Mechanisms initiating integrin-stimulated flow recruitment in arteriolar networks. / Frame, Mary D.; Rivers, Richard; Altland, Owen; Cameron, Scott.

In: Journal of Applied Physiology, Vol. 102, No. 6, 06.2007, p. 2279-2287.

Research output: Contribution to journalArticle

Frame, Mary D. ; Rivers, Richard ; Altland, Owen ; Cameron, Scott. / Mechanisms initiating integrin-stimulated flow recruitment in arteriolar networks. In: Journal of Applied Physiology. 2007 ; Vol. 102, No. 6. pp. 2279-2287.
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