Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries

P. Coats, Fiona Johnston, John MacDonald, John J. McMurray, Chris Hillier

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In this study we have examined for the first time the signal transduction mechanisms involved in the generation of pressure-dependent myogenic tone in human small resistance arteries from the subcutaneous vascular bed. Methods: Myogenic responses and the subcellular mechanisms involved in the generation of this response were studied on a pressure myograph. Human subcutaneous resistance arteries constricted 14.1±1.1% in response to an increases in intraluminal pressure from 40 to 80 mmHg and a further 3.5±1.7% in response to the 80–120-mmHg pressure step. Ca2+ depletion or nifedipine abolished this response, whereas BAY K 8644 increased this response to 20.6±2.1% (P<0.05, response vs. control). The phospholipase C inhibitor U-73122 reduced the myogenic response to 2.5±1.0% at 80 mmHg (P<0.01, response vs. control) and abolished it at 120 mmHg. Diacylglycerol lipase inhibition with RHC-80267 abolished all myogenic responses to pressure. The protein kinase C (PKC) activator phorbol 12,13-dibutyerate increased the maximal myogenic response to 20.9±1.8% (P<0.05, response vs. control), whereas the PKC inhibitor calphostin C abolished myogenic responses. These data show that the generation of pressure-dependent myogenic tone in human subcutaneous arteries is dependent on Ca2+ influx via voltage operated Ca2+ channels (VOCCs) and a concomitant requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC.
LanguageEnglish
Pages828-837
Number of pages10
JournalCardiovascular Research
Volume49
Issue number4
DOIs
Publication statusPublished - Mar 2001

Fingerprint

Arteries
Pressure
Protein Kinase C
Type C Phospholipases
Diacylglycerol Kinase
Lipoprotein Lipase
Protein C Inhibitor
Nifedipine
Protein Kinase Inhibitors
Blood Vessels
Signal Transduction

Keywords

  • signal transduction
  • calcium
  • microcirculation contractile function
  • protein kinases
  • Ca-channel

Cite this

Coats, P. ; Johnston, Fiona ; MacDonald, John ; McMurray, John J. ; Hillier, Chris. / Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries. In: Cardiovascular Research. 2001 ; Vol. 49, No. 4. pp. 828-837.
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Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries. / Coats, P.; Johnston, Fiona; MacDonald, John; McMurray, John J.; Hillier, Chris.

In: Cardiovascular Research, Vol. 49, No. 4, 03.2001, p. 828-837.

Research output: Contribution to journalArticle

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