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- Title
Local L-NAME Administration Blocks Insulin-Mediated but not Contraction-Mediated Capillary Recruitment in Rat Hindleg Muscles.
- Authors
Bradley, Eloise A.; Ross, Renee M.; Clark, Michael G.; Mcconell, Glenn K.; Rattigan, Stephen
- Abstract
Exercise and insulin each increase the delivery of hormones and nutrients to skeletal muscle by increasing capillary recruitment in vivo in rats and humans. Insulin's ability to recruit capillaries is lost in insulin resistant states while contraction-mediated recruitment is normal, indicating that the two stimuli use different signaling pathways. The insulin stimulus appears to involve NO as systemic nitric oxide synthase (NOS) inhibition has been shown to block capillary recruitment but the contraction stimulus is unknown. However previous NOS inhibition results are inconclusive due to the systemic alterations in blood pressure and the central nervous system interactions that occur with whole body administration of NOS inhibitors. In this study the effect of local one hindleg administration of the NOS inhibitor, L-NAME (5-10µM) via retrograde infusion into the epigastric artery was made during either a 3mU⋅min[sup -1]⋅kg[sup -1] euglycemic insulin clamp or while the muscles were being contracted (35V field stimulation, 0.1 msec pulses at 2Hz). The contra-lateral non-infused hindleg acted as control for the experiments. Systemic blood pressure and heart rate, femoral blood flow, and muscle capillary recruitment were measured in both test and control legs. Local L-NAME infusion had no effect on blood pressure, heart rate and femoral blood flow in the control leg indicating that the effects of NOS inhibition were restricted to the treated leg. Insulin- and contraction-mediated increases in femoral blood flow were both reduced by L-NAME treatment. Insulin significantly (P<0.05) increased capillary recruitment by 42% and muscle contraction increased capillary recruitment by 185%. L-NAME treatment completely inhibited the insulin-mediated capillary recruitment in the test leg without affecting the control leg but had no effect on contraction-mediated capillary recruitment. These experiments confirm that insulin-mediated capillary recruitment is dependent on NO. In contrast contraction-mediated capillary recruitment is either not NO dependent or the loss of NO is compensated by other contraction-mediated processes. Future resolution of the contraction-mediated stimuli will be important as it may provide a drug target to overcome the loss of insulin-mediated capillary recruitment in insulin resistance and diabetes.
- Subjects
CONTACT inhibition; NITRIC-oxide synthases; CAPILLARIES; INSULIN resistance; HINDLIMB; LABORATORY rats
- Publication
Diabetes, 2007, Vol 56, pA397
- ISSN
0012-1797
- Publication type
Article