Coats, P. and Johnston, Fiona and MacDonald, John and McMurray, John J. and Hillier, Chris (2001) Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries. Cardiovascular Research, 49 (4). pp. 828-837. ISSN 0008-6363Full text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||signal transduction , calcium , microcirculation contractile function , protein kinases, Ca-channel , Pharmacy and materia medica, Physiology, Cardiology and Cardiovascular Medicine, Physiology (medical)|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||27 Feb 2012 11:35|
|Last modified:||29 Apr 2016 08:48|