Aging enhances contraction to thromboxane A(2) in aorta from female senescence-accelerated mice

作者：Novella Susana; Paula Dantas Ana; Segarra Gloria; Novensa Laura; Heras Magda; Hermenegildo Carlos; Medina Pascual^*

来源：Age, 2013, 35(1): 117-128.

DOI：10.1007/s11357-011-9337-y

• U46619
• NO bioavailability
• Contractile prostanoids
• Vascular reactivity

The time-course for aging-associated effects on vascular reactivity to U46619, a stable analogue of thromboxane A(2) (TXA(2)), was studied in aorta from female senescence-accelerated mice-prone (SAMP8), a murine model of accelerated senescence. SAMP8 and senescence-accelerated mice-resistant (SAMR1) were divided into three groups: 3-, 6- and 10-month-old. Contractile curves to U46619 (10(-9) to 10(-6) M) were performed in aortic rings in the absence or in the presence of nitric oxide synthase (NOS) inhibitor N-G-nitro-l-arginine methyl ester (l-NAME; 10(-4) M) and/or cyclooxygenase (COX) inhibitor indomethacin (10(-5) M). Protein and gene expression for COX-1 and COX-2 were determined by immunofluorescence and real-time PCR, respectively. Maximal contraction to U46619 was markedly higher in SAMP8 at all ages. In SAMR1, increases were seen at 10 months, while SAMP8 displays augmented contraction at 6 months, which was further increased at 10 months. l-NAME enhanced U46619 contractions in both 6-month-old groups, although the increase was higher on vessels from SAMR1 at this age. Indomethacin equally increased U46619 contractions in both 3-month-old groups, suggesting the production of vasodilator prostaglandin in young animals. In contrast, at 6 and 10 months indomethacin decreased U46619 contractions in both groups, indicating an aging-associated swap to a release of contractile prostanoids in aorta. In conclusion, aging enhances contractile responses to TXA(2) in aorta from female mice by a mechanism involving a decrease of NO production and increased action of contractile prostanoids. This process occurs earlier in SAMP8 mice, establishing these mice as good model to study cardiovascular aging in a convenient and standard time-course.

• 出版日期2013-2