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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 agematched uninfected mice using a pressure myograph. We tested responses to the α1-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. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (CMV) is implicated in vascular complications through endothelial dysfunction. However, the effect of in vivo infections on vascular function in isolated arteries has not been examined. In pregnancy, systemic and uterine vascular adaptations accommodate increased blood volume through several mechanisms, including decreased sensitivity to vasoconstrictors and increased production of endothelial-dependent vasodilators. We hypothesized that an active in vivo CMV infection would reduce vasodilation of isolated arteries to the endothelial-dependent vasodilator methacholine and increase vasoconstriction to the α1-adrenergic receptor agonist phenylephrine and that these CMV-induced changes would be accentuated in late pregnancy. A mouse CMV infection model was used to study vascular responses in isolated mesenteric and uterine arteries from nonpregnant and late pregnant mice. In the mouse, CMV is not transmitted to the fetus. Accordingly, there was no evidence of active infection in any fetus examined, even though an active infection was found in salivary glands, uterine and mesenteric arteries, and placentas. Contrary to our hypothesis, increased endothelial-dependent vasodilation was found in mesenteric arteries from infected compared with uninfected non- pregnant and pregnant mice These data implicate active CMV infections in hypotensive disorders. Similarly, increased vasodilation was found in uterine arteries from infected vs. uninfected nonpregnant mice. However, this was completely reversed in infected compared with uninfected late pregnant mice in which vasodilation in uterine arteries was significantly reduced. Uterine arteries from infected pregnant mice also showed increased vasoconstriction to phenylephine. Maternal infection led to decreased placental weights but had no effect on fetal weights in late pregnancy. These novel data demonstrate abnormal systemic and uterine vascular responses during an active CMV infection in both nonpregnant and late pregnant mice. Importantly, despite reduced placental weights, fetal weights were maintained, suggesting effective intrauterine compensation in the mouse model. [ABSTRACT FROM AUTHOR]