The senescence-accelerated mouse (SAM-P8) as a model for the study of vascular functional alterations during aging.
We studied vascular function in quiescent aortas from senescence-accelerated resistant (SAM-R1) and prone (SAM-P8) mice. Myographical studies of thoracic aorta segments from 6-7 month-old mice showed that the contractility of SAM-P8 aortas was markedly higher than that of SAM-R1 after KCl depolarization or phenylephrine addition. Acetylcholine dose-response relaxation curves revealed that SAM-R1 vessels were slightly more sensitive than those of SAM-P8. In the presence of the NO synthase inhibitor, L-NAME, all vessels displayed contractions to acetylcholine, but these were more distinct in the SAM-R1. Phenylephrine plus L-NAME displayed stronger contractions in both animal strains, but were markedly more pronounced in SAM-R1. The cyclooxygenase inhibitor, indomethacin did not change the vessel responses to acetylcholine or phenylephrine. These data indicate that NO synthase, not cyclooxygenase, was responsible for the differences in contractility. Standard histology and immunohistochemistry of endothelial NO synthase revealed no differences in the expression of this protein. In contrast, increased levels of malondialdehyde were found in SAM-P8 vessels. We conclude that SAM-P8 vessels exhibit higher contractility than those of SAM-R1. Furthermore, our results suggest that the endothelium of SAM-P8 vessels is dysfunctional and lacks normal capability to counteract smooth muscle contraction. Therefore, our findings support SAM-P8 as a suitable model for the study of vascular physiological changes during aging.
Lloréns
Silvia
S
Departamento de Ciencias Médicas, Facultad de Medicina and Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Almansa, 14, 02006 Albacete, Spain.
de Mera
Raquel M Melero-Fernandez
RM
Pascual
Alejandro
A
Prieto-Martín
Ana
A
Mendizábal
Yolanda
Y
de Cabo
Carlos
C
Nava
Eduardo
E
Jordán
Joaquín
J
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology