Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries.
OBJECTIVE
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.


CONCLUSIONS
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. Ca(2+) 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-dibutyrate 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 Ca(2+) influx via voltage operated Ca(2+) channels (VOCCs) and a concomitant requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC.
Coats
P
P
School of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Scotland, Glasgow, UK. p.coats@gcal.ac.uk
Johnston
F
F
MacDonald
J
J
McMurray
J J
JJ
Hillier
C
C
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000368:Aged; D000704:Analysis of Variance; D001158:Arteries; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D003512:Cyclohexanones / Q000494:pharmacology; D004791:Enzyme Inhibitors; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D009281:Naphthalenes; D011760:Pyrrolidinones; D019837:Ryanodine Receptor Calcium Release Channel; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D015240:Phorbol 12,13-Dibutyrate; D002110:Caffeine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D011493:Protein Kinase C; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; C058819:calphostin C; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid