Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus infections

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 304; no. 2; p. H183
• Main Authors: Gombos, R B, Brown, J C, Teefy, J, Gibeault, R L, Conn, K L, Schang, L M, Hemmings, D G
• Format: Journal Article
• Language: English
• Published: United States 15-01-2013
• Subjects: Age Factors; Aging; Animals; Cytomegalovirus - physiology; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - metabolism; Cytomegalovirus Infections - physiopathology; Cytomegalovirus Infections - virology; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fertility; Infertility - physiopathology; Infertility - virology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - metabolism; Mesenteric Arteries - physiopathology; Mice; Mice, Inbred C57BL; Myography; Nitric Oxide - metabolism; Pregnancy; Pregnancy Rate; Prostaglandins - metabolism; Uterine Artery - drug effects; Uterine Artery - metabolism; Uterine Artery - physiopathology; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Virus Latency
• ISSN: 1522-1539
• DOI: 10.1152/ajpheart.00461.2012

Human cytomegalovirus (HCMV) is associated with vascular diseases in both immunosuppressed and immunocompetent individuals. CMV infections cycle between active and latent phases throughout life. We and others have shown vascular dysfunction during active mouse CMV (mCMV) infections. Few studies have examined changes in physiology during latent CMV infections, particularly vascular responses or whether the negative effects of aging on vascular function and fertility will be exacerbated under these conditions. We measured vascular responses in intact mesenteric and uterine arteries dissected from young, mid-aged, and aged latently mCMV-infected (mCMV genomes are present but infectious virus is undetectable) and age-matched uninfected mice using a pressure myograph. We tested responses to the α(1)-adrenergic agonist phenylephrine, the nitric oxide donor sodium nitroprusside, and the endothelium-dependent vasodilator methacholine. In young latently mCMV-infected mice, vasoconstriction was increased and vasodilation was decreased in mesenteric arteries, whereas both vasoconstriction and vasodilation were increased in uterine arteries compared with those in age-matched uninfected mice. In reproductively active mid-aged latently infected mice, mesenteric arteries showed little change, whereas uterine arteries showed greatly increased vasoconstriction. These vascular effects may have contributed to the decreased reproductive success observed in mid-aged latently mCMV-infected compared with age-matched uninfected mice (16.7 vs. 46.7%, respectively). In aged latently infected mice, vasodilation is increased in mesenteric and uterine arteries likely to compensate for increased vasoconstriction to mediators other than phenylephrine. The novel results of this study show that even when active mCMV infections become undetectable, vascular dysfunction continues and differs with age and artery origin.