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. Results and conclusion: 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.