%0 Journal Article %1 Beetz2009 %A Beetz, N. %A Harrison, M. D. %A Brede, M. %A Zong, X. %A Urbanski, M. J. %A Sietmann, A. %A Kaufling, J. %A Barrot, M. %A Seeliger, M. W. %A Vieira-Coelho, M. A. %A Hamet, P. %A Gaudet, D. %A Seda, O. %A Tremblay, J. %A Kotchen, T. A. %A Kaldunski, M. %A Nusing, R. %A Szabo, B. %A Jacob, H. J. %A Cowley, Jr. %A Biel, M. %A Stoll, M. %A Lohse, M. J. %A Broeckel, U. %A Hein, L. %D 2009 %J J Clin Invest %K Acid Adult Aged Alleles Amino Animals Base Blood C3H C57BL Cardiovascular DNA/genetics Data Epinephrine/physiology Eye Female GTP-Binding Homozygote Humans Hypertension/etiology/genetics/*physiopathology/*prevention Knockout Male Mice Middle Models, Molecular Nervous Neurosecretory Nucleotide Phenotype Phosphoproteins/chemistry/deficiency/*genetics/*physiology Physiological Polymorphism, Pressure/genetics/physiology Protein Proteins/chemistry/*genetics/*physiology Regulators/chemistry/deficiency/*genetics/*physiology Sequence Single Stress, Sympathetic System/*physiopathology Systems/physiopathology control %N 12 %P 3597-3612 %T Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19959875 %V 119 %X Hypertension and its complications represent leading causes of morbidity and mortality. Although the cause of hypertension is unknown in most patients, genetic factors are recognized as contributing significantly to an individual's lifetime risk of developing the condition. Here, we investigated the role of the G protein regulator phosducin (Pdc) in hypertension. Mice with a targeted deletion of the gene encoding Pdc (Pdc-/- mice) had increased blood pressure despite normal cardiac function and vascular reactivity, and displayed elevated catecholamine turnover in the peripheral sympathetic system. Isolated postganglionic sympathetic neurons from Pdc-/- mice showed prolonged action potential firing after stimulation with acetylcholine and increased firing frequencies during membrane depolarization. Furthermore, Pdc-/- mice displayed exaggerated increases in blood pressure in response to post-operative stress. Candidate gene-based association studies in 2 different human populations revealed several SNPs in the PDC gene to be associated with stress-dependent blood pressure phenotypes. Individuals homozygous for the G allele of an intronic PDC SNP (rs12402521) had 12-15 mmHg higher blood pressure than those carrying the A allele. These findings demonstrate that PDC is an important modulator of sympathetic activity and blood pressure and may thus represent a promising target for treatment of stress-dependent hypertension.

@article{Beetz2009, abstract = {Hypertension and its complications represent leading causes of morbidity and mortality. Although the cause of hypertension is unknown in most patients, genetic factors are recognized as contributing significantly to an individual's lifetime risk of developing the condition. Here, we investigated the role of the G protein regulator phosducin (Pdc) in hypertension. Mice with a targeted deletion of the gene encoding Pdc (Pdc-/- mice) had increased blood pressure despite normal cardiac function and vascular reactivity, and displayed elevated catecholamine turnover in the peripheral sympathetic system. Isolated postganglionic sympathetic neurons from Pdc-/- mice showed prolonged action potential firing after stimulation with acetylcholine and increased firing frequencies during membrane depolarization. Furthermore, Pdc-/- mice displayed exaggerated increases in blood pressure in response to post-operative stress. Candidate gene-based association studies in 2 different human populations revealed several SNPs in the PDC gene to be associated with stress-dependent blood pressure phenotypes. Individuals homozygous for the G allele of an intronic PDC SNP (rs12402521) had 12-15 mmHg higher blood pressure than those carrying the A allele. These findings demonstrate that PDC is an important modulator of sympathetic activity and blood pressure and may thus represent a promising target for treatment of stress-dependent hypertension.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Beetz, N. and Harrison, M. D. and Brede, M. and Zong, X. and Urbanski, M. J. and Sietmann, A. and Kaufling, J. and Barrot, M. and Seeliger, M. W. and Vieira-Coelho, M. A. and Hamet, P. and Gaudet, D. and Seda, O. and Tremblay, J. and Kotchen, T. A. and Kaldunski, M. and Nusing, R. and Szabo, B. and Jacob, H. J. and Cowley, Jr. and Biel, M. and Stoll, M. and Lohse, M. J. and Broeckel, U. and Hein, L.}, biburl = {https://www.bibsonomy.org/bibtex/2fd29bd7bae183f628202659e6767dcea/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {976bf828d4dd5471ada9138bec2633e6}, intrahash = {fd29bd7bae183f628202659e6767dcea}, issn = {1558-8238 (Electronic) 1558-8238 (Linking)}, journal = {J Clin Invest}, keywords = {Acid Adult Aged Alleles Amino Animals Base Blood C3H C57BL Cardiovascular DNA/genetics Data Epinephrine/physiology Eye Female GTP-Binding Homozygote Humans Hypertension/etiology/genetics/*physiopathology/*prevention Knockout Male Mice Middle Models, Molecular Nervous Neurosecretory Nucleotide Phenotype Phosphoproteins/chemistry/deficiency/*genetics/*physiology Physiological Polymorphism, Pressure/genetics/physiology Protein Proteins/chemistry/*genetics/*physiology Regulators/chemistry/deficiency/*genetics/*physiology Sequence Single Stress, Sympathetic System/*physiopathology Systems/physiopathology control}, month = Dec, note = {Beetz, Nadine Harrison, Michael D Brede, Marc Zong, Xiangang Urbanski, Michal J Sietmann, Anika Kaufling, Jennifer Barrot, Michel Seeliger, Mathias W Vieira-Coelho, Maria Augusta Hamet, Pavel Gaudet, Daniel Seda, Ondrej Tremblay, Johanne Kotchen, Theodore A Kaldunski, Mary Nusing, Rolf Szabo, Bela Jacob, Howard J Cowley, Allen W Jr Biel, Martin Stoll, Monika Lohse, Martin J Broeckel, Ulrich Hein, Lutz HL082798/HL/NHLBI NIH HHS/United States In Vitro Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States The Journal of clinical investigation J Clin Invest. 2009 Dec;119(12):3597-3612.}, number = 12, pages = {3597-3612}, shorttitle = {Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice}, timestamp = {2010-12-14T18:22:13.000+0100}, title = {Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19959875}, volume = 119, year = 2009 }