Adiponectin Receptor Agonist, AdipoRon, Causes Vasorelaxation Predominantly Via a Direct Smooth Muscle Action
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 .
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AdipoRon has been proposed for treatment of type 2 diabetes and other obesity-related disorders in mice.
“AdipoRon has first been proposed for the treatment of type 2 diabetes and other obesity-related disorders in mice [32,106,107,108,137,138].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [108]
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- Authors
- Hong, K., Lee, S., Li, R., Yang, Y., Tanner, M. A., Wu, J., & Hill, M. A.
- Affiliations
- University of Missouri (US)
- Incheon National University (KR)
- Southwest Medical University (CN)
- Corresponding author
- Hill, Michael A.
- Venue
- Microcirculation
- Publisher
- Wiley
- Published
- 2016-04
- Volume
- 23
- Issue
- 3
- Pages
- 207-220
- ISSN
- 1073-9688 (ISSN-L)
- 1549-8719
- OpenAlex
- W2231147116
- Cited by
- 30
- References
- 37
- Citations by year
- 2026: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 1
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microcirculation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RO1 HL085119)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- AdipoRon, adiponectin receptor agonist, vasorelaxation, vasodilation, vascular smooth muscle cells, endothelium-independent relaxation, AMPK, potassium currents, intracellular calcium, adiponectin, cerebral arteries, coronary arteries, skeletal muscle arteries, insulin resistance
- MeSH terms
- Animals, Male, Muscle, Smooth, Vascular, Piperidines, Vasodilation, Rats, Sprague-Dawley, Calcium Signaling, Mice, Rats, Receptors, Adiponectin
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