PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists
We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα) agonists using isolated mouse aortas and middle cerebral arteries (MCAs). The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pre...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/302495 |
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| author | Neerupma Silswal Nikhil K. Parelkar Michael J. Wacker Mostafa Badr Jon Andresen |
| author_facet | Neerupma Silswal Nikhil K. Parelkar Michael J. Wacker Mostafa Badr Jon Andresen |
| author_sort | Neerupma Silswal |
| collection | DOAJ |
| description | We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα) agonists using isolated mouse aortas and middle cerebral arteries (MCAs). The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP) channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC), and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC) activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response. |
| format | Article |
| id | doaj-art-04eaa85b702b45b5806aab413e266ecf |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-04eaa85b702b45b5806aab413e266ecf2025-02-03T01:23:52ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/302495302495PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα AgonistsNeerupma Silswal0Nikhil K. Parelkar1Michael J. Wacker2Mostafa Badr3Jon Andresen4Muscle Biology Research Group (MUBIG), Basic Medical Science Department, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USAMuscle Biology Research Group (MUBIG), Basic Medical Science Department, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USAMuscle Biology Research Group (MUBIG), Basic Medical Science Department, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USADivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USAMuscle Biology Research Group (MUBIG), Basic Medical Science Department, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USAWe sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα) agonists using isolated mouse aortas and middle cerebral arteries (MCAs). The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP) channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC), and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC) activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response.http://dx.doi.org/10.1155/2012/302495 |
| spellingShingle | Neerupma Silswal Nikhil K. Parelkar Michael J. Wacker Mostafa Badr Jon Andresen PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists PPAR Research |
| title | PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists |
| title_full | PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists |
| title_fullStr | PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists |
| title_full_unstemmed | PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists |
| title_short | PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists |
| title_sort | pparα independent arterial smooth muscle relaxant effects of pparα agonists |
| url | http://dx.doi.org/10.1155/2012/302495 |
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