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doi:10.1016/j.yexmp.2006.10.001    
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Copyright © 2006 Elsevier Inc. All rights reserved.

Gender differences in endothelial function and inflammatory markers along the occurrence of pathological events in stroke-prone rats

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Rossana Ballerioa, Elisabetta Gianazzab, c, d, Luciana Mussonib, Ingrid Millere, Paolo Gelosab, Uliano Guerrinib, Ivano Eberinib, c, d, Manfred Gemeinere, Silvia Belcreditob, d, Elena Tremolia, b and Luigi Sironib, d, Corresponding Author Contact Information, E-mail The Corresponding Author

aCentro Cardiologico “Monzino”, IRCCS, Milano, Italy

bDipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Italy

cGruppo di Studio per la Proteomica e la Struttura delle Proteine, Università degli Studi di Milano, Italy

dCentro di Eccellenza per le Malattie Neurodegenerative, Università degli Studi di Milano, Italy

eInstitut für Medizinische Chemie, Department für Naturwissenschaften Veterinärmedizinische Universität, Wien, Austria


Received 2 October 2006; 
revised 2 October 2006. 
Available online 5 December 2006.

Abstract

Spontaneously hypertensive stroke-prone rats (SHRSP) feature an established model for human cerebrovascular disease. SHRSP, kept on a high-salt permissive diet (JPD), develop hypertension, renal and brain damage. In this report we compared the behavior of female and male SHRSP regarding the main aspects of their pathological condition. Brain abnormalities, detected by magnetic resonance imaging, developed spontaneously in males after 42 ± 3 days, in females after 114 ± 14 days from the start of JPD. Survival was > 3-fold longer for females than for males. The development of brain damage was preceded, in both genders, by an inflammatory condition characterized by the accumulation in serum and urine of acute-phase proteins. The increase in thiostatin level was significantly lower and delayed in female in comparison to male SHRSP. During JPD female and male SHRSP developed massive proteinuria, its worsening being significantly slower in females. The alterations of vasculature-bound barriers in kidney and brain were connected with endothelial dysfunction and relative deficiency in nitric oxide (NO). In thoracic aortic rings, basal release of NO was significantly higher in female than in male SHRSP, both if receiving and if not receiving JPD. The gender differences in SHRSP thus appear to be connected to a more efficient control in females of inflammation and of endothelial dysfunction.

Keywords: Stroke-prone rats; Gender differences; Inflammation; Vasculature; Endothelial function

Article Outline

Introduction
Materials and methods
Animals and treatments
MRI evaluations
Electrophoretic techniques and statistical analysis of the data
Ex vivo tests on aortic segments
Results
Survival rate
Proteomes of the biological fluids
Vascular function
Discussion
Acknowledgements
References







Corresponding Author Contact InformationCorresponding author. Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, via Balzaretti 9, I-20133 Milano, Italy. Fax: +39 2 50318250.

 
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