Cytomegalovirus promotes microvascular dysfunction through alterations in the cyclooxygenase pathway of arachidonic acid metabolism

Cytomegalovirus (CMV) is a beta‐herpesvirus that has been implicated in cardiovascular disease. Like other cardiovascular risk factors, CMV infection leads to impaired arteriolar vasodilation to acetylcholine (ACh) before large vessel disease is apparent. Furthermore, this virus exacerbates hypercholesterolemia (HC)‐induced arteriolar dysfunction. We previously found that indomethacin, a cyclooxygenase (COX) inhibitor, reduced vasodilation in mock‐inoculated mice but not in CMV‐infected mice. We hypothesized that CMV and CMV+HC elicit microvascular dysfunction by altering the balance of COX‐1 and COX‐2 enzymes, and therefore their metabolites. To test this, C57Bl/6J mice were infected with CMV or mock inoculum. HC diet was introduced at 5 wks. At 11 wks post infection, intravital microscopy was performed to measure arteriolar vasoreactivity to ACh in the cremaster muscle. A specific COX‐2 inhibitor (NS‐398) impaired vasodilation in mock mice but not in either CMV group. In contrast, SC‐560 inhibition of COX‐1 had no effect on mocks but partially restored vasodilation in CMV mice. Our findings indicate that CMV disrupts the balance of AA metabolites produced via COX, and suggest that CMV infection leads to enhanced generation of vasoconstrictors from COX‐1 and/or reduced COX‐2 derived vasodilators. Future work will identify the metabolites involved in this process. (NIHP20RR018724, AHA0730294N)