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Vasoconstrictor stimulus determines the functional contribution of myoendothelial feedback to mesenteric arterial tone.

Authors
  • Wei, R1
  • Lunn, S E1
  • Tam, R1
  • Gust, S L1
  • Classen, B1
  • Kerr, P M2
  • Plane, F1, 3
  • 1 Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. , (Canada)
  • 2 Department of Nursing Science, Faculty of Nursing, MacEwan University, Edmonton, Alberta, T5J 4S2, Canada. , (Canada)
  • 3 Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. , (Canada)
Type
Published Article
Journal
The Journal of Physiology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Apr 01, 2018
Volume
596
Issue
7
Pages
1181–1197
Identifiers
DOI: 10.1113/JP274797
PMID: 29411383
Source
Medline
Keywords
License
Unknown

Abstract

Constriction of isolated resistance arteries in response to α1 -adrenoceptor agonists is limited by reciprocal engagement of inhibitory endothelial mechanisms via myoendothelial feedback. In the current model of feedback, agonist stimulation of smooth muscle cells results in localized InsP3 -dependent Ca2+ transients that activate endothelial IKCa channels. The subsequent hyperpolarization of the endothelial membrane potential then feeds back to the smooth muscle to limit further reductions in vessel diameter. We hypothesized that the functional contribution of InsP3 -IKCa channel-mediated myoendothelial feedback to limiting arterial diameter may be influenced by the nature of the vasoconstrictor stimulus. To test this hypothesis, we investigated the functional role of myoendothelial feedback in modulating responses of rat mesenteric resistance arteries to the adrenoceptor agonist noradrenaline, the thromboxane A2 mimetic U46619, increases in intravascular pressure and stimulation of perivascular sympathetic nerves. In isolated arteries, responses to noradrenaline and stimulation of sympathetic nerves, but not to U46619 and increases in intravascular pressure, were modulated by IKCa channel-dependent myoendothelial feedback. In the intact mesenteric bed perfused under conditions of constant flow, responses to exogenous noradrenaline were modulated by myoendothelial feedback, but shear stress-induced release of NO and activation of endothelial SKCa channels appeared to be the primary mediators of endothelial modulation of vasoconstriction to agonists and nerve stimulation. Thus, we propose that myoendothelial feedback may contribute to local control of diameter within arterial segments, but at the level of the intact vascular bed, increases in shear stress may be the major stimulus for engagement of the endothelium during vasoconstriction.

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