AHEART Apr. 45/4

Jensen, Michael E., and Edward J. Messina. C-peptide induces a concentration-dependent dilation of skeletal muscle arterioles only in presence of insulin. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H1223–H1228, 1999.—In this study we tested the hypothesis that C-peptide alone or in conjunction with insulin may cause a dilation of skeletal muscle arterioles. First-order arterioles (88 μm) isolated from rat cremaster muscles were pressurized (65 mmHg), equilibrated in a Krebs bicarbonate-buffered solution (pH 7.4), gassed with 10% O2 (balance 5% CO2, 85% N2), and studied in a no-flow state. C-peptide administered at concentrations of 0.3, 1, 3, 10, 100, 300, and 1,000 ng/ml evoked arteriolar dilation that was not concentration dependent. In contrast, the administration of the four lower physiological concentrations of C-peptide to arterioles exposed to a nondilating concentration of insulin evoked a significant concentrationdependent increase in arteriolar diameter from 8.6 to 42.3% above control. The arteriolar dilation to C-peptide in the presence of insulin was completely inhibited by administration of NG-nitro-L-arginine (1024 M). Responses to ACh and adenosine were not enhanced when these drugs were administered in the presence of insulin. These results indicate that C-peptide has the capacity to evoke arteriolar dilation in skeletal muscle via a nitric oxide-mediated mechanism that appears to be enhanced by an interaction with insulin. Furthermore, the effects of insulin appear to be specific for C-peptide and are not the result of a general enhancement of endothelium-dependent or endothelium-independent dilation.