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Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression.

Abstract：

:The present study investigated the time-course for aging-associated effects on contractile and relaxing vascular responses and nitric oxide (NO) production in the aorta from female senescence-accelerated resistant (SAMR1) and prone (SAMP8) mice. Both SAMR1 and SAMP8 were studied at three different ages: 3 (young), 6 (middle age) and 10 (old) months. Concentration-response curves to phenylephrine (10(-8) to 10(-5) M) or acetylcholine (10(-9) to 10(-5) M) were performed in the aortic rings in the absence or in the presence of NO synthase (NOS) inhibitor L-NAME (10(-4) M). Protein and gene expression for endothelial NOS (eNOS) was determined by immunofluorescence, Western blot and real-time PCR. Although we have not seen any difference in vascular responses when comparing both strains at 3 months old, we found a significant aging-associated impairment of vascular reactivity that follows a distinct time-course in SAMR1 and SAMP8. In SAMR1, increases in phenylephrine contraction and decreases in acetylcholine relaxation were only seen at 10 months old, while SAMP8 displays altered responses at 6 months that are further impaired at 10 months old. L-NAME treatment enhanced phenylephrine contractions and completely inhibited acetylcholine relaxations in all age groups of SAMR1 and SAMP8. However, the magnitude of increase in phenylephrine contraction by L-NAME was markedly reduced by aging and followed a faster pace in SAMP8. Similar pattern of responses was observed in the time course for changes of eNOS expression, suggesting an earlier and more pronounced aging-associated decrease of NO production and eNOS expression in SAMP8. These results reveal that aging enhances contractile responses to phenylephrine and decreases endothelium-dependent relaxation to acetylcholine in the aorta from female mice by a mechanism that involves a decrease of NO production. This process occurs earlier in the aorta from SAMP8 mice, establishing these mice as suitable model to study cardiovascular aging in a convenient and standard time course.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Novella S,Dantas AP,Segarra G,Vidal-Gómez X,Mompeón A,Garabito M,Hermenegildo C,Medina P

doi

10.1016/j.exger.2013.08.003

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

1329-37

issue

eissn

0531-5565

issn

1873-6815

pii

S0531-5565(13)00240-4

journal_volume

pub_type

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Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression.