Journal article
Interference with peroxisome proliferator-activated receptor-γ in vascular smooth muscle causes baroreflex impairment and autonomic dysfunction
Hypertension (Dallas, Tex. 1979), Vol.64(3), pp.590-596
09/2014
DOI: 10.1161/HYPERTENSIONAHA.114.03553
PMCID: PMC4134389
PMID: 24914194
Abstract
S-P467L mice expressing dominant negative peroxisome proliferator-activated receptor-γ selectively in vascular smooth muscle exhibit impaired vasodilation, augmented vasoconstriction, hypertension, and tachycardia. We hypothesized that tachycardia in S-P467L mice is a result of baroreflex dysfunction. S-P467L mice displayed increased sympathetic traffic to the heart and decreased baroreflex gain and effectiveness. Carotid arteries exhibited inward remodeling but no changes in distensibility or stress/strain. Aortic depressor nerve activity in response to increased arterial pressure was blunted in S-P467L mice. However, the arterial pressure and heart rate responses to aortic depressor nerve stimulation were unaltered in S-P467L mice, suggesting that the central and efferent limbs of the baroreflex arc remain intact. There was no transgene expression in nodose ganglion and no change in expression of the acid-sensing ion channel-2 or -3 in nodose ganglion. There was a trend toward decreased expression of transient receptor potential vanilloid-1 receptor mRNA in nodose ganglion, but no difference in the immunochemical staining of transient receptor potential vanilloid-1 receptor in the termination area of the left aortic depressor nerve in S-P467L mice. Although there was no difference in the maximal calcium response to capsaicin in cultured nodose neurons from S-P467L mice, there was decreased desensitization of transient receptor potential vanilloid-1 receptor channels. In conclusion, S-P467L mice exhibit baroreflex dysfunction because of a defect in the afferent limb of the baroreflex arc caused by impaired vascular function, altered vascular structure, or compromised neurovascular coupling. These findings implicate vascular smooth muscle peroxisome proliferator activated receptor-γ as a critical determinant of neurovascular signaling.
Details
- Title: Subtitle
- Interference with peroxisome proliferator-activated receptor-γ in vascular smooth muscle causes baroreflex impairment and autonomic dysfunction
- Creators
- Giulianna R Borges - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityDonald A Morgan - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityPimonrat Ketsawatsomkron - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityAaron D Mickle - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityAnthony P Thompson - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityMartin D Cassell - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityDurga P Mohapatra - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityKamal Rahmouni - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa CityCurt D Sigmund - From the Department of Pharmacology (G.R.B., D.A.M., P.K., A.D.M., D.P.M., K.R., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C.), and Center on the Functional Genomics of Hypertension (K.R., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City. curt-sigmund@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.64(3), pp.590-596
- Publisher
- United States
- DOI
- 10.1161/HYPERTENSIONAHA.114.03553
- PMID
- 24914194
- PMCID
- PMC4134389
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- F31 CA171927 / NCI NIH HHS T32 NS045549 / NINDS NIH HHS R01 HL061446 / NHLBI NIH HHS R01 HL048058 / NHLBI NIH HHS P01 HL062984 / NHLBI NIH HHS P01 HL084207 / NHLBI NIH HHS R37 HL048058 / NHLBI NIH HHS R01 NS069898 / NINDS NIH HHS
- Language
- English
- Date published
- 09/2014
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040012302771
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