IMPAIRED ARTERIAL REACTIVITY FOLLOWING CYTOMEGALOVIRUS-INFECTION IN THE IMMUNOSUPPRESSED RAT

1 Cytomegalovirus (CMV) is a major pathogen in immunocompromised indiv iduals and may participate in the pathogenesis of atherosclerosis in t he general population. We evaluated whether CMV-infection alters the f unction of arterial smooth muscle. 2 Blood pressure (BP) and arterial reactivity were recorded in immunosuppressed rats that had been infect ed with CMV (10(5) plaque forming units i.p.). Furthermore, the reacti vity of isolated arteries was compared between CMV-infected rats and r ats injected with bacterial endotoxin (LPS). 3 Initially resting BP an d heart rate (HR) were not modified in CMV-infected rats, but barorefl ex control of HR was impaired. By the eighth day post-CMV, BP dropped precipitously and could no longer be raised by phenylephrine (PHE). 4 In mesenteric resistance arteries, isolated at this stage from CMV-inf ected rats, contractile responses to nerve stimulation, noradrenaline, PHE and 5-hydroxytryptamine (5-HT) were virtually absent while those to high potassium and vasopressin (AVP) were not modified. In aortae o f CMV-infected rats, responses to 5-HT and AVP were impaired while tho se to PHE or potassium were hardly affected. Reduced contractile respo nses could not be restored by N-G-nitro-L-arginine methyl ester (L-NAM E). 5 Continuous treatment of CMV-infected rats with prazosin (0.1 mg kg(-1) day(-1)) prevented blood pressure lowering and resistance arter y changes. 6 Observations in arteries of LPS-treated rats (5-10 mg kg( -1), i.p.) differed markedly from those in vessels of Ch?V-infected an imals. The contractile reactivity of their mesenteric resistance arter ies was not altered while in their aortae, responses to PHE, 5-HT and AVP were reduced. With the exception of the AVP responses, this was mo re pronounced in the presence of L-arginine and reversed by L-NAME. 7 These findings indicate that CMV-infection results in a reduction of r esistance artery reactivity and hypotonia. This seems not to involve c ytokine-mediated induction of NO synthase in the vascular wall but may be due to alterations of excitation-contraction coupling in arterial smooth muscle in response to increased sympathetic nervous input.