C-peptide induces a concentration-dependent dilation of skeletal muscle arterioles only in presence of insulin.
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 microm) 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 concentration-dependent 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 (10(-4) 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.
Jensen
M E
ME
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA. ej_messina@nymc.edu
Messina
E J
EJ
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002096:C-Peptide / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D019335:Nitroarginine / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002096:C-Peptide; D004791:Enzyme Inhibitors; D007328:Insulin; D007329:Insulin Antagonists; D014665:Vasodilator Agents; D019335:Nitroarginine; D000241:Adenosine; D000109:Acetylcholine