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Research was conducted to study the vascular and cardiac response of nitric oxide synthase blockade in vivo in rats. Blood pressure was determined by tail-cuff plethysmography in conscious, restrained rats while the aorta was dissected and prepared for aortic rings for functional studies. Results indicated that nitric oxide deficiency in vivo results in the development of vascular and cardiac hypertrophy. They also showed that no significant difference in nitric oxide expression in the aorta or heart despite marked functional and structural changes.

Abstract Rationale Nitric oxide is an important regulator of vascular tone in the pulmonary circulation. Surgical correction of congenital heart disease limits pulmonary hypertension to a brief period. Objectives The study has measured expression of endothelial (eNOS), inducible (iNOS), and neuronal nitric oxide synthase (nNOS) in the lungs from biopsies of infants with pulmonary hypertension secondary to cardiac abnormalities (n = 26), compared to a control group who did not have pulmonary or cardiac disease (n = 8). Methods eNOS, iNOS and nNOS were identified by immunohistochemistry and quantified in specific cell types. Measurements and main results Significant increases of eNOS and iNOS staining were found in pulmonary vascular endothelial cells of patients with congenital heart disease compared to control infants. These changes were confined to endothelial cells and not present in other cell types. Patients who strongly expressed eNOS also had strong expression of iNOS. Conclusion Upregulation of eNOS and iNOS occurs at an early stage of pulmonary hypertension, and may be a compensatory mechanism limiting the rise in pulmonary artery pressure.

The article presents a study on the diagnostic accuracy of bright-blood T2-weighted cardiac magnetic resonance imaging (MRI) for myocardial hemorrhage in experimental myocardial infarction (MI) in swine. The study involved 15 swine where MI was created by occluding the left anterior descending or circumflex coronary arteries. Findings reportedly indicate that bright-blood T2-weighted MRI has a high diagnostic accuracy for myocardial hemorrhage.

The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)-induced arrhythmias via nitric oxide (NO) and peroxynitrite.In sham-operated rats, the effects of in vivo administration of a bolus dose of AM (1 nmol kg−1) was assessed on arterial blood pressure (BP), ex vivo leukocyte reactive oxygen species generation and nitrotyrosine deposition (a marker for peroxynitrite formation) in the coronary endothelium.In pentobarbitone-anaesthetized rats subjected to ligation of the left main coronary artery for 30 min, the effects of a bolus dose of AM (1 nmol kg−1, i.v.; n=19) or saline (n=18) given 5 min pre-occlusion were assessed on the number and incidence of cardiac arrhythmias. In a further series of experiments, some animals received infusions of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA) (0.5 mg kg−1 min−1) or the peroxynitrite scavenger N-mercaptopropionyl-glycine (MPG) (20 mg kg−1 h−1) before AM.AM treatment significantly reduced mean arterial blood pressure (MABP) and increased ex vivo chemiluminescence (CL) generation from leukocytes in sham-operated animals. AM also enhanced the staining for nitrotyrosine in the endothelium of coronary arteries.AM significantly reduced the number of total ventricular ectopic beats that occurred during ischaemia (from 1185±101 to 520±74; P<0.05) and the incidences of ventricular fibrillation (from 61 to 26%; P<0.05). AM also induced a significant fall in MABP prior to occlusion. AM-induced cardioprotection was abrogated in animals treated with the NO synthase inhibitor LNNA and the peroxynitrite scavenger MPG.This study has shown that AM exhibits an antiarrhythmic effect through a mechanism that may involve generation of NO and peroxynitrite.British Journal of Pharmacology (2006) 148, 599–609. doi:10.1038/sj.bjp.0706771; published online 22 May 2006 [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study was to examine neointima formation in balloon injured left subclavian artery of rabbits subjected to two different methods of leukocyte depletion at the time of injury. Methods: Angioplasty of the left subclavian artery was performed in leukopenic male New Zealand White rabbits. Depletion of circulating leukocytes was induced by either mustine hydrochloride or an antibody against leukocyte common antigen (anti-LCA) before angioplasty. Left and right subclavian arteries were removed 28 days after injury for morphological analysis and measurement of neointimal size. At the same time, leukocytes were isolated from autologous rabbit blood for 51Cr-labelling for assessment of leukocyte adhesion to injured and non-injured artery segments. Results: Leukopenia decreased neointima formation in injured arteries (neointimal area was 0.09±0.03 mm2 in mustine-treated arteries, n = 8, vs. 0.56±0.07 mm2 in control arteries, n = 7; P<0.001 and 0.07±0.01 mm2 in anti-LCA treated arteries, n = 9, vs. 0.22±0.04 mm2 in non immune serum-treated arteries, n = 9; P<0.001). Adventitial fibrosis was also significantly (P<0.05) decreased by both leukopenic interventions. Neither medial nor adventitial area was modified in any of the groups. No differences in leukocyte adhesion were observed between injured and non-injured arteries in any of the experimental groups at the 28 day time point. Conclusion: These results suggest that leukocytes play a major role in the development of two of the major characteristics of the response to balloon injury, namely formation of neointima and adventitial fibrosis, that currently limit the success of clinical angioplasty. Elucidation of the fine mechanisms involved in leukocyte-mediated injury may lead to the discovery of novel therapeutic targets for the prevention of restenosis. [ABSTRACT FROM PUBLISHER]