Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression.
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.
['Novella|Susana|S|', 'Dantas|Ana Paula|AP|', 'Segarra|Gloria|G|', 'Vidal-Gómez|Xavier|X|', 'Mompeón|Ana|A|', 'Garabito|Manel|M|', 'Hermenegildo|Carlos|C|', 'Medina|Pascual|P|']
D000109:Acetylcholine D000375:Aging D000818:Animals D001013:Aorta, Thoracic D004730:Endothelium, Vascular D005260:Female D015870:Gene Expression D051379:Mice D023421:Models, Animal D019331:NG-Nitroarginine Methyl Ester D009569:Nitric Oxide D052250:Nitric Oxide Synthase Type III D009599:Nitroprusside D010656:Phenylephrine D014661:Vasoconstriction
Aging Vascular reactivity Endothelium-dependent relaxation Adrenergic Female aging animal model NO bioavailability