Inhibition of Inducible Nitric Oxide Synthesis Ameliorates Liver lschemia and Reperfusion Injury Induced Transient Increase in Arterial Stiffness

Purpose. Hemodynamic instability is a frequent scenario after reperfusion of ischemic liver due to major liver resection and liver transplantation. Previously, we showed that liver ischemia/reperfusion (I/R) injury induced increases in reactive oxygen/nitrogen species and inducible nitric oxide synthase (iNOS) expression impaired cardiac contractility. In addition, nitric oxide (NO) generated via iNOS may have impacts on large arterial smooth muscle tone, causing transient changes in arterial stiffness and ventricular afterload. In this study, we aim to investigate associations between iNOS and transient alternation in arterial stiffness during Jiver I/R injury, and effects of treatments with 1400W, a selective iNOS inhibitor, and L-NG nitroarginine methyl ester (L-NAME), a non-specific NOS inhibitor. Methods. The arterial stiffness is evaluated using the pulse wave velocity (PWV2), measured by finding the means of two high-fidelity micromanometers positioned at the aortic root and left femoral artery. Liver ischemia was conducted by occluding both the hepatic artery and portal vein for 30 minutes, followed by 120 minutes of reperfusion. Studies were performed on male Sprague-Dawley rats in four groups: a sham-operated group, a liver I/R group, and those groups pretreated with 1400W (N-[3-(aminomethyl) benzyl]acetamidine) or L-NAME. Serum NO metabolites, tumor necrosis factor-a (TNF-alpha) and methylguanidine (MG) were measured at baseline, 30 minutes of ischemia, and 120 minutes of reperfusion. Results. Post-reperfusion arterial stiffness increased by similar to 14% as compared with the baseline, along with increases in serum NO metabolites, TNF-alpha, and MG level (P < .05); 1400W and L-NAME treatment reduces post-reperfusion arterial stiffness by similar to 5% similarly. Treatments with 1400W and L-NAME both attenuated I/R induced increases in serum TNF-alpha, MG, and NO metabolites level (P < .05). Conclusions. I/R-induced arterial stiffening was strongly associated with increased systemic inflammation. Comparable effects with treatments of 1400W and L-NAME suggested that iNOS plays a dominant role in I/R-induced transient arterial stiffening.