title: Comparison of endothelial function, O2-* and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice.
abstract: Vascular aging is characterized by decreased nitric oxide (NO) bioavailability, oxidative stress, and enhanced apoptotic cell death. We hypothesized that interspecies comparative assessment of vascular function among rodents with disparate longevity may offer insight into the mechanisms determining successful vascular aging. We focused on four rodents that show approximately an order of magnitude range in maximum longevity (ML). The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known (ML > 28 yr), Damara mole rats (DMRs, Cryptomys damarensis; ML approximately 16 yr) and guinea pigs (GPs, Cavia porcellus; ML approximately 6 yr) have intermediate longevity, whereas laboratory mice are short living (ML approximately 3.5 yr). We compared interspecies differences in endothelial function, O(2)(-)* and H(2)O(2) production, and resistance to apoptotic stimuli in blood vessels. Sensitivity to acetylcholine-induced, NO-mediated relaxation was smaller in carotid arteries from NMRs, GPs, and DMRs than in mouse vessels. Measurements of production of O(2)(-)* (lucigenin chemiluminescence and ethidium bromide fluorescence) and H(2)O(2) (dichlorofluorescein fluorescence) showed that free radical production in vascular endothelial and smooth muscle cells is comparable in vessels of the three longer-living species and in arteries of shorter-living mice. In mouse arteries, H(2)O(2) (from 10(-6) to 10(-3) mol/l) and heat exposure (42 degrees C for 15-45 min) enhanced apoptotic cell death, as indicated by an increased DNA fragmentation rate and increased caspase 3/7 activity. In NMR vessels, only the highest doses of H(2)O(2) enhanced apoptotic cell death, whereas heat exposure did not increase DNA fragmentation rate. Interspecies comparison showed there is a negative correlation between H(2)O(2)-induced apoptotic cell death and ML. Thus endothelial vasodilator function and vascular production of reactive oxygen species do not correlate with maximal lifespan, whereas increased lifespan potential is associated with an increased vascular resistance to proapoptotic stimuli.
authors.affiliation: Dept. of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Nazar
authors.initials: N
authors.lastname: Labinskyy
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Orosz
authors.forename: Kira
authors.initials: K
authors.lastname: Smith
authors.forename: Aracelie
authors.initials: A
authors.lastname: Rivera
authors.forename: Rochelle
authors.initials: R
authors.lastname: Buffenstein
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008136:Longevity; D051379:Mice; D008810:Mice, Inbred C57BL; D019577:Mole Rats; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000109:Acetylcholine; D010100:Oxygen