nitroarginine and dorsomorphin

To investigate the effects of activation of the AMP-activated protein kinase (AMPK) on muscle perfusion and to elucidate the mechanisms involved.. In a combined approach, we studied the vasoactive actions of AMPK activator by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on rat cremaster muscle resistance arteries ( approximately 100 mum) ex vivo and on microvascular perfusion in the rat hindlimb in vivo. In isolated resistance arteries, AICAR increased Thr172 phosphorylation of AMPK in arteriolar endothelium, which was predominantly located in microvascular endothelium. AICAR induced vasodilation (19+/-4% at 2 mmol/L, P<0.01), which was abolished by endothelium removal, inhibition of NO synthase (with N-nitro-L-arginine), or AMPK (with compound C). Smooth muscle sensitivity to NO, determined by studying the effects of the NO donor S-nitroso-N-acetylpenicillamine (SNAP), was not affected by AICAR except at the highest dose. AICAR increased endothelial nitric oxide synthase activity, as indicated by Ser1177 phosphorylation. In vivo, infusion of AICAR markedly increased muscle microvascular blood volume (approximately 60%, P<0.05), as was evidenced by contrast-enhanced ultrasound, without effects on blood pressure, femoral blood flow, or hind leg glucose uptake.. Activation of AMPK by AICAR activates endothelial nitric oxide synthase in arteriolar endothelium by increasing its Ser1177 phosphorylation, which leads to vasodilation of resistance arteries and recruitment of microvascular perfusion in muscle.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Arteries; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Activation; Enzyme Activators; Enzyme Inhibitors; Hindlimb; Infusions, Intravenous; Microcirculation; Muscle, Skeletal; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase Type III; Nitroarginine; Phosphorylation; Pyrazoles; Pyrimidines; Rats; Regional Blood Flow; Ribonucleotides; S-Nitroso-N-Acetylpenicillamine; Serine; Threonine; Time Factors; Vascular Resistance; Vasodilation; Vasodilator Agents