Cardiac impairment and nitric oxide synthase activity in the chronic portal vein-stenosed rat

Decreased cardiac contractility and beta-adrenergic responses have been obs erved in the chronic portal vein-stenosed (PVS) rat. Because nitric oxide ( NO) may be increased in PVS and has been recognized as a negative inotropic agent, we investigated the induction of NO synthase (NOS2) and/or changes in constitutive NOS (NOS3) as factors in the cardiac dysfunction of the PVS rat. Ten to twelve days after portal vein stenosis or sham operation, card iac function was evaluated in paced left ventricular papillary muscles (LVP M) and right ventricular strips (RV). To determine if NO modulation of cont ractile function was altered in PVS, we examined the increase in developed tension produced by the effect of N-omega-nitro-L-arginine (L-NNA) on the m yocardial force-frequency relationship. Cardiac tissue NOS2 and NOS3 activi ties were assayed, Western blot analyses of NOS2 and NOS3 expression were p erformed, and circulating nitrate-nitrite (NOX) levels (an indicator of in vivo NOS activity) were assayed. Basal LVPM and RV contractile indexes were significantly reduced in PVS (30-50%), without a change in the relaxation rate. No between-group differences in the cardiac NOS2 or NOS3 enzymatic ac tivities of PVS and sham-operated (SO) rats were observed. Western blots re vealed no cardiac NOS2 expression in either SO or PVS rats. In contrast, NO S3 was expressed in both SO and PVS rats, but there was no quantitative dif ference in expression between the two groups. Changes in the cardiac force- frequency relationship (staircase effect) after L-NNA were consistent with NOS3 modulation of contractile function in both SO and PVS rats, but there was no between-group difference in the modulation. Circulating NOX concentr ations did not differ between SO and PVS rats. In conclusion, protein expre ssion data, enzymatic assays, end-product assays, and functional data indic ate that between-group differences in NOS2 and NOS3 activity are not respon sible for the cardiac impairment that has been observed in the chronic PVS rat.