Format

Send to

Choose Destination
Microcirculation. 2016 Apr;23(3):207-20. doi: 10.1111/micc.12266.

Adiponectin Receptor Agonist, AdipoRon, Causes Vasorelaxation Predominantly Via a Direct Smooth Muscle Action.

Hong K1,2, Lee S2,3, Li R2,4, Yang Y2, Tanner MA2, Wu J2,4, Hill MA1,2.

Author information

1
Department of Medical Pharmacology & Physiology, University of Missouri-Columbia, Columbia, Missouri, USA.
2
Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri, USA.
3
Division of Sport Science & Sport Science Institute, Incheon National University, Incheon, South Korea.
4
Drug Discovery Research Center, Luzhou Medical College, Luzhou, China.

Abstract

OBJECTIVE:

AdipoRon, an adiponectin receptor agonist, was recently proposed for treating insulin resistance and hyperglycemia. As adiponectin is vasoprotective via NO-mediated signaling, it was hypothesized that adipoRon similarly exerts potentially beneficial vasodilator effects. We therefore examined if adipoRon induces vasorelaxation and via what contributing mechanisms.

METHODS:

Vascular function was assessed in skeletal muscle arteries from rats and cerebral/coronary arteries from mice using pressure and wire myography.

RESULTS:

Using qPCR, mRNA for adiponectin receptors was demonstrated in skeletal muscle, cerebral and coronary arteries. AdipoRon-caused vasorelaxation was not abolished by compound C (10 μM; AMPK inhibitor). Inhibition of endothelium-dependent relaxation with combinations of l-NAME/indomethacin/apamin/TRAM-34 only slightly reduced adipoRon-mediated vasorelaxation in cerebral and coronary arteries. EC-denuded cremaster arteries showed similar relaxant responses to adipoRon as in intact vessels, suggesting adipoRon directly impacts VSMCs. K(+) currents measured in VSMCs isolated from mouse basilar and LAD arteries were not altered by adiopRon. In cremaster arteries, adipoRon induced vasorelaxation without a marked decrease in VSMC [Ca(2+)]i . Adiponectin, itself, caused vasodilation in intact cremaster arteries while failing to cause significant dilation in EC-denuded arteries, consistent with endothelium dependency of adiponectin.

CONCLUSIONS:

AdipoRon exerts vasodilation by mechanisms distinct to adiponectin. The dominant mechanism for adipoRon-induced vasorelaxation occurs independently of endothelium-dependent relaxing factors, AMPK activation, K(+) efflux-mediated hyperpolarization and reductions in cytosolic [Ca(2+)]i .

KEYWORDS:

adiponectin; adiponectin receptors; endothelial independent; relaxation; vascular smooth muscle

PMID:
26728950
DOI:
10.1111/micc.12266
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center