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Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle

Premilovac, D ORCID: 0000-0003-2770-4713, Attrill, E, Rattigan, S ORCID: 0000-0001-6172-3040, Richards, SM ORCID: 0000-0002-5988-0423, Kim, JA and Keske, MA ORCID: 0000-0003-4214-7628 2018 , 'Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle' , Cardiovascular Research , pp. 1-12 , doi: 10.1093/cvr/cvy225.

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Abstract

Aims:Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin's microvascular and metabolic actions in skeletal muscle.Methods and Results:Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinemic euglycemic clamp) or insulin (hyperinsulinemic euglycemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinemic euglycemic clamp) infusion. In all animals systemic metabolic effects, central hemodynamics, femoral artery blood flow, microvascular blood flow and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinemic euglycemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin's effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow and this was accompanied by reduced skeletal muscle glucose uptake.Conclusions:Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin's microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

Item Type: Article
Authors/Creators:Premilovac, D and Attrill, E and Rattigan, S and Richards, SM and Kim, JA and Keske, MA
Keywords: microvascular blood flow, muscle metabolism, angiotensin II
Journal or Publication Title: Cardiovascular Research
Publisher: Elsevier Science Bv
ISSN: 0008-6363
DOI / ID Number: 10.1093/cvr/cvy225
Copyright Information:

Copyright The Author(s) 2018.

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