Gender differences in endothelial function and inflammatory markers along the occurrence of pathological events in stroke-prone rats.
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.
Ballerio
Rossana
R
Centro Cardiologico Monzino, IRCCS, Milano, Italy.
Gianazza
Elisabetta
E
Mussoni
Luciana
L
Miller
Ingrid
I
Gelosa
Paolo
P
Guerrini
Uliano
U
Eberini
Ivano
I
Gemeiner
Manfred
M
Belcredito
Silvia
S
Tremoli
Elena
E
Sironi
Luigi
L
D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D001798:Blood Proteins / Q000032:analysis; D001921:Brain / Q000098:blood supply; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006973:Hypertension / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply; D007704:Kininogens / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011918:Rats, Inbred SHR; D012737:Sex Factors; D013997:Time Factors
D000209:Acute-Phase Proteins; D015415:Biomarkers; D001798:Blood Proteins; D007704:Kininogens; D009569:Nitric Oxide