Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 559631.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Smooth muscle-specific deletion of nitric oxide-sensitive guanylyl cyclase is sufficient to induce hypertension in mice
Authors:Groneberg, D.; Konig, P.; Wirth, A.; Offermanns, S.; Koesling, D.; Friebe, A.
Title of Journal:Circulation
Volume:121
Issue / Number:3
Start Page:401
End Page:9
Audience:Not Specified
Abstract / Description:BACKGROUND: Arterial hypertension is one of the major diseases in industrial countries and a major cause of mortality. One of the main vascular factors responsible for the relaxation of blood vessels and regulation of blood pressure is nitric oxide (NO). NO acts predominantly via NO-sensitive guanylyl cyclase (NO-GC), which is made up of 2 different subunits (alpha and beta). Deletion of the beta(1) subunit leads to a global NO-GC knockout, and these mice are hypertensive. However, global deletion of NO-GC in mice does not allow identification of the cell/tissue type responsible for the elevated blood pressure. METHODS AND RESULTS: To determine the relative contribution of smooth muscle cells to the hypertension seen in NO-GC knockout mice, we generated smooth muscle-specific knockout mice for the beta(1) subunit of NO-GC using a tamoxifen-inducible system. Male mice were investigated because the Cre transgene used is located on the Y chromosome. Tamoxifen injection led to a rapid reduction of NO-GC expression in smooth muscle but did not affect that in other tissues. Parallel to a reduction in NO-induced cGMP accumulation, NO-induced relaxation of aortic smooth muscle was gradually lost after induction by tamoxifen. Concomitantly, these animals developed hypertension within 3 to 4 weeks. CONCLUSIONS: We generated a model in which the development of hypertension can be visualized over time by deletion of a single gene in smooth muscle cells. In sum, our data provide evidence that deletion of NO-GC solely in smooth muscle is sufficient to cause hypertension.
Free Keywords:Animals; Blood Platelets/enzymology; Blood Pressure/physiology; Brain/enzymology; Cyclic GMP/metabolism; Disease Models, Animal; Endothelium-Dependent Relaxing Factors/metabolism; Gene Expression/drug effects; Guanylate Cyclase/*genetics/*metabolism; Hypertension/*metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular/*enzymology; Nitric Oxide/*metabolism; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors/pharmacology; Piperazines/pharmacology; Protein Subunits/genetics/metabolism; Purines/pharmacology; Receptors, Cytoplasmic and Nuclear/*genetics/*metabolism; Sulfones/pharmacology; Tamoxifen; Transgenes/genetics; Vasodilation/physiology
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Physiologisches Institut I, Universitat Wurzburg, Wurzburg, Germany.
Identifiers:ISSN:1524-4539 (Electronic) 0009-7322 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.