M Gil-Ortega1, C F García-Prieto1, G Ruiz-Hurtado2,3, C Steireif2,4, M C González5, A Schulz4, R Kreutz4, M S Fernández-Alfonso2, S Arribas5, B Somoza1. 1. Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU - San Pablo, Madrid, Spain. 2. Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense, Madrid, Spain. 3. Instituto de Investigación imas12, Hospital Universitario 12 de Octubre, Madrid, Spain. 4. Department of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin, Berlin, Germany. 5. Departamento de Fisiología, Universidad Autónoma, Madrid, Spain.
Abstract
BACKGROUND AND PURPOSE: The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling. EXPERIMENTAL APPROACH: Experiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensive rats (SHR). KEY RESULTS: Incremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower β-values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains. CONCLUSION AND IMPLICATIONS: These data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries.
BACKGROUND AND PURPOSE: The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling. EXPERIMENTAL APPROACH: Experiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensiverats (SHR). KEY RESULTS: Incremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower β-values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains. CONCLUSION AND IMPLICATIONS: These data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries.
Authors: Gary F Mitchell; Germaine C Verwoert; Kirill V Tarasov; Aaron Isaacs; Albert V Smith; Ernst R Rietzschel; Toshiko Tanaka; Yongmei Liu; Afshin Parsa; Samer S Najjar; Kevin M O'Shaughnessy; Sigurdur Sigurdsson; Marc L De Buyzere; Martin G Larson; Mark P S Sie; Jeanette S Andrews; Wendy S Post; Francesco U S Mattace-Raso; Carmel M McEniery; Gudny Eiriksdottir; Patrick Segers; Ramachandran S Vasan; Marie Josee E van Rijn; Timothy D Howard; Patrick F McArdle; Abbas Dehghan; Elizabeth S Jewell; Stephen J Newhouse; Sofie Bekaert; Naomi M Hamburg; Anne B Newman; Albert Hofman; Angelo Scuteri; Dirk De Bacquer; Mohammad Arfan Ikram; Bruce M Psaty; Christian Fuchsberger; Matthias Olden; Louise V Wain; Paul Elliott; Nicholas L Smith; Janine F Felix; Jeanette Erdmann; Joseph A Vita; Kim Sutton-Tyrrell; Eric J G Sijbrands; Serena Sanna; Lenore J Launer; Tim De Meyer; Andrew D Johnson; Anna F C Schut; David M Herrington; Fernando Rivadeneira; Manuela Uda; Ian B Wilkinson; Thor Aspelund; Thierry C Gillebert; Luc Van Bortel; Emelia J Benjamin; Ben A Oostra; Jingzhong Ding; Quince Gibson; André G Uitterlinden; Gonçalo R Abecasis; John R Cockcroft; Vilmundur Gudnason; Guy G De Backer; Luigi Ferrucci; Tamara B Harris; Alan R Shuldiner; Cornelia M van Duijn; Daniel Levy; Edward G Lakatta; Jacqueline C M Witteman Journal: Circ Cardiovasc Genet Date: 2011-11-08
Authors: M Victoria Conde; M Carmen Gonzalez; Begoña Quintana-Villamandos; Fatima Abderrahim; Ana M Briones; Luis Condezo-Hoyos; Javier Regadera; Cristina Susin; Jose J Gomez de Diego; Emilio Delgado-Baeza; Juan J Diaz-Gil; Silvia M Arribas Journal: Am J Physiol Heart Circ Physiol Date: 2011-06-03 Impact factor: 4.733
Authors: Angela Schulz; Sabrina Schütten-Faber; Nicole van Es; Johannes Unland; Leonard Schulte; Peter Kossmehl; Emile de Heer; Reinhold Kreutz Journal: Physiol Genomics Date: 2011-11-22 Impact factor: 3.107
Authors: Cesar Cerezo; Luis M Ruilope; Julian Segura; Jose A Garcia-Donaire; Juan J de la Cruz; Jose R Banegas; Bernard Waeber; Ton J Rabelink; Franz H Messerli Journal: J Hypertens Date: 2012-01 Impact factor: 4.844
Authors: Simone Gschwend; Marcel Bernhard Haug; Marc Nierhaus; Angela Schulz; Roland Vetter; Peter Kossmehl; Hans-Dieter Orzechowski; Jürgen Scholze; Lars Rothermund; Reinhold Kreutz Journal: Life Sci Date: 2009-07-25 Impact factor: 5.037
Authors: M K Szymanski; J H Buikema; D J van Veldhuisen; J Koster; J van der Velden; N Hamdani; J L Hillege; R G Schoemaker Journal: Basic Res Cardiol Date: 2012-01-19 Impact factor: 17.165
Authors: Helena Pulido-Olmo; Elena Rodríguez-Sánchez; José Alberto Navarro-García; María G Barderas; Gloria Álvarez-Llamas; Julián Segura; Marisol Fernández-Alfonso; Luis M Ruilope; Gema Ruiz-Hurtado Journal: Front Immunol Date: 2017-07-24 Impact factor: 7.561
Authors: Piotr Skrzypczyk; Anna Maria Wabik; Michał Szyszka; Sergiusz Józwiak; Przemysław Bombiński; Aleksandra Jakimów-Kostrzewa; Michał Brzewski; Małgorzata Pańczyk-Tomaszewska Journal: Front Pediatr Date: 2021-11-29 Impact factor: 3.418
Authors: Raquel González-Blázquez; Beatriz Somoza; Marta Gil-Ortega; Miriam Martín Ramos; David Ramiro-Cortijo; Elena Vega-Martín; Angela Schulz; Luis Miguel Ruilope; Peter Kolkhof; Reinhold Kreutz; María S Fernández-Alfonso Journal: Front Pharmacol Date: 2018-10-09 Impact factor: 5.810
Authors: Elena Vega-Martín; Marta Gil-Ortega; Raquel González-Blázquez; Sara Benedito; Jesús Fernández-Felipe; Mariano Ruiz-Gayo; Nuria Del Olmo; Julie A Chowen; Laura M Frago; Beatriz Somoza; María S Fernández-Alfonso Journal: Nutrients Date: 2021-03-19 Impact factor: 5.717