Broughton, B. R.S., Miller, A. A. and Sobey, C. G. (2010) Endothelium-dependent relaxation by G protein-coupled receptor 30 agonists in rat carotid arteries. AJP: Heart and Circulatory Physiology, 298(3), H1055-H1061. (doi: 10.1152/ajpheart.00878.2009) (PMID:20061543)
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Abstract
Recent studies have identified that the novel membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), is present in blood vessels. However, the signaling mechanisms associated with GPR30 in the vasculature remain unclear. We examined whether putative agonists of GPR30 exert vasorelaxant and/or antioxidant effects similar to those reported for estrogen. Using wire myography, we assessed the role of the endothelium in relaxation responses to the GPR30 agonists, G-1 and 5408-0877 (1 nM-10 μM), in U-46619-precontracted common carotid arteries from Sprague-Dawley rats. Furthermore, using lucigenin (5 μM)-enhanced chemiluminescence, we tested the effect of G-1 (10 μM) on superoxide levels. Specific immunofluorescence was also used to confirm GPR30 expression in the arterial wall. We found that G-1 and 5408-0877 induced a concentration-dependent relaxation in carotid arteries from both male and female rats. Interestingly, G-1- and 5408-0877-induced relaxation was abolished by endothelium removal and abrogated in the presence of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (100 μM). In addition, G-1 significantly decreased NADPH (100 μM)-stimulated superoxide production by carotid and intracranial (pooled basilar and middle cerebral) arteries but also attenuated the superoxide signal detected in a cell-free xanthine/xanthine oxidase assay. Furthermore, GPR30 immunoreactivity was observed in endothelial and vascular smooth muscle cells of carotid arteries from both genders. These findings indicate that GPR30 is expressed throughout the arterial wall and that GPR30 agonists elicit endothelial-derived nitric oxide-dependent relaxation of the carotid artery in male and female rats. Additionally, G-1 appears to directly scavenge superoxide anion.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Miller, Dr Alyson |
| Authors: | Broughton, B. R.S., Miller, A. A., and Sobey, C. G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | AJP: Heart and Circulatory Physiology |
| Publisher: | American Physiological Society |
| ISSN: | 0363-6135 |
| ISSN (Online): | 1522-1539 |
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