Effects of central administration of insulin or L-NMMA on rat skeletal muscle microvascular perfusion
Bradley, EA and Willson, KJ and Choi-Lundberg, D and Clark, MG and Rattigan, S, Effects of central administration of insulin or L-NMMA on rat skeletal muscle microvascular perfusion, Diabetes Obesity & Metabolism, 12, (10) pp. 900-908. ISSN 1462-8902 (2010) [Refereed Article]
Aim: Intracerebroventricular (ICV) administration of a nitric oxide synthase (NOS) inhibitor to rats has been reported to raise blood pressure (BP)
and cause insulin resistance, suggestive of a central effect of insulin that is NO dependent. Herein we test whether ICV insulin has peripheral
haemodynamic and metabolic effects and whether peripheral effects of systemic insulin are affected by the ICV administration of the NOS
inhibitor NG-methyl-L-arginine (L-NMMA).
Methods: Anaesthetized rats were fitted with an ICV cannula for insulin, artificial cerebrospinal fluid (aCSF) or L-NMMA infusion. Rats receiving
ICV L-NMMA (500 ìg) underwent systemic insulin clamp (10 mU/min/kg) or saline treatment for 70 min and were compared with animals
receiving an equal amount of L-NMMA infused systemically.
Results: ICV aCSF or insulin (135 mU/min/kg brain) for 70 min or systemic L-NMMA (500 ìg) had no effect on BP, heart rate (HR), femoral
blood flow (FBF), glucose infusion rate, muscle 2-deoxyglucose uptake, microvascular perfusion or plasma insulin. However, ICV L-NMMA
reduced systemic insulin-mediated increases in FBF (2.05 ± 0.08 to 1.55 ± 0.15 ml/min), 2-deoxyglucose uptake (17.7 ± 0.15 to 10.0 ±
0.03 ìg/g/min) and microvascular perfusion (10.5 ± 0.5 to 6.6 ± 1.1 mol/min) (each mean ± SE, p < 0.05); plasma insulin, HR and BP were
Conclusions: Central insulin administration had no effect on skeletal muscle haemodynamics or glucose metabolism. However, systemic
insulin-mediated increases in limb blood flow, muscle microvascular perfusion and glucose uptake may be regulated by a central pathway that
is NO dependent.