BACKGROUND: Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Frömter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations of endothelial function under conditions of increased albuminuria. Our aim was to investigate if the MWF strain shows generalized endothelial dysfunction or endothelial dysfunction localized to the coronary vascular bed, and if so, determine which endothelial dilative mediators are involved. METHODS: Coronary and mesenteric arteries were investigated for endothelium-dependent relaxation and the contribution of prostacyclin, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in MWF rats compared to normal Wistar rats. In addition, as MWF rats show increased blood pressure, spontaneously hypertensive rats (SHR) with similar hypertension but without increased albuminuria also were studied. RESULTS: Maximal total endothelium-dependent relaxation of coronary arteries was strongly impaired in MWF rats (55 +/- 3%) compared to Wistar (89 +/- 5%) and SHR (89 +/- 2%) P < 0.05, respectively. The NO-mediated relaxation as well as the relaxation mediated by EDH were significantly lower in coronary arteries from MWF compared to Wistar. In mesenteric arteries of MWF the endothelium-dependent relaxation was intact. CONCLUSIONS: The strong impairment of coronary endothelium-dependent relaxation in the MWF model of spontaneous albuminuria may be due to defects in production or activity of NO and EDH. The intact mesenteric endothelium-dependent relaxation suggests that increased albuminuria may not be related to generalized endothelial vasodilator dysfunction in this model. Selective impairment of coronary endothelial function in a setting of spontaneous albuminuria may be a feature of the MWF that may be employed to further study cause-effect relations between albuminuria and coronary artery disease.
BACKGROUND:Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Frömter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations of endothelial function under conditions of increased albuminuria. Our aim was to investigate if the MWF strain shows generalized endothelial dysfunction or endothelial dysfunction localized to the coronary vascular bed, and if so, determine which endothelial dilative mediators are involved. METHODS: Coronary and mesenteric arteries were investigated for endothelium-dependent relaxation and the contribution of prostacyclin, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in MWF rats compared to normal Wistar rats. In addition, as MWF rats show increased blood pressure, spontaneously hypertensiverats (SHR) with similar hypertension but without increased albuminuria also were studied. RESULTS: Maximal total endothelium-dependent relaxation of coronary arteries was strongly impaired in MWF rats (55 +/- 3%) compared to Wistar (89 +/- 5%) and SHR (89 +/- 2%) P < 0.05, respectively. The NO-mediated relaxation as well as the relaxation mediated by EDH were significantly lower in coronary arteries from MWF compared to Wistar. In mesenteric arteries of MWF the endothelium-dependent relaxation was intact. CONCLUSIONS: The strong impairment of coronary endothelium-dependent relaxation in the MWF model of spontaneous albuminuria may be due to defects in production or activity of NO and EDH. The intact mesenteric endothelium-dependent relaxation suggests that increased albuminuria may not be related to generalized endothelial vasodilator dysfunction in this model. Selective impairment of coronary endothelial function in a setting of spontaneous albuminuria may be a feature of the MWF that may be employed to further study cause-effect relations between albuminuria and coronary artery disease.
Authors: M Gil-Ortega; C F García-Prieto; G Ruiz-Hurtado; C Steireif; M C González; A Schulz; R Kreutz; M S Fernández-Alfonso; S Arribas; B Somoza Journal: Br J Pharmacol Date: 2015-07-21 Impact factor: 8.739
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: Beatriz Gálvez-Prieto; Beatriz Somoza; Marta Gil-Ortega; Concha F García-Prieto; Ana I de Las Heras; M Carmen González; Silvia Arribas; Isabel Aranguez; Juliane Bolbrinker; Reinhold Kreutz; Mariano Ruiz-Gayo; Maria S Fernández-Alfonso Journal: Front Pharmacol Date: 2012-06-05 Impact factor: 5.810
Authors: Yumei Wang; Sjoerd Landheer; Wiek H van Gilst; Aart van Amerongen; Hans-Peter Hammes; Robert H Henning; Leo E Deelman; Hendrik Buikema Journal: PLoS One Date: 2012-10-10 Impact factor: 3.240
Authors: Iryna V Samarska; Hjalmar R Bouma; Hendrik Buikema; Hubert E Mungroop; Martin C Houwertjes; Anthony R Absalom; Anne H Epema; Robert H Henning Journal: PLoS One Date: 2014-05-12 Impact factor: 3.240
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