Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries

Objective: In this study we have examined for the first time the signal tra nsduction mechanisms involved in the generation of pressure-dependent myoge nic 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. Resul ts 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 i ncreased this response to 20.6+/-2.1% (P<0.05, response vs, control). The p hospholipase C inhibitor U-73122 reduced the myogenic response to 2.5+/-1.0 % at 80 mmHg (P<0.001, response vs, control) and abolished it at 120 mmHg. Diacylglycerol lipase inhibition with RHC-80267 abolished all myogenic resp onses to pressure. The protein kinase C (PKC) activator phorbol 12,13-dibut yerate increased the maximal myogenic response to 20.9+/-1.8% (P<0.05, resp onse vs. control), whereas the PKC inhibitor calphostin C abolished myogeni c responses. These data show that the generation of pressure-dependent myog enic tone in human subcutaneous arteries is dependent on Ca2+ influx via vo ltage operated Ca2+ channels (VOCCs) and a concomitant requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC. (C) 2001 Else vier Science B.V. All rights reserved.