Validation of noninvasive morphological and diffusion imaging in mouse emphysema by micro-computed tomography and hyperpolarized (129)Xe magnetic resonance imaging.

Animal disease models are pivotal in investigating the pathogenesis of emphysema and developing novel drugs, but the modalities to evaluate murine emphysema models have been of limited validity and sensitivity. In this study, we evaluated hyperpolarized (129)Xe magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) compared with traditional methods, such as plethysmography and histology. Elastase-treated mice and adiponectin knockout mice were used as murine emphysema models to evaluate these modalities. Three weeks after elastase administration, significant and heterogeneous emphysema was evaluated according to the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, as examined by micro-CT, correlated with the mean linear intercept and plethysmography parameters in whole lungs. These correlations were also observed in regional areas. Furthermore, we introduced hyperpolarized (129)Xe MRI, which can evaluate gas exchange between the alveoli and blood during spontaneous breathing. Parameters of gas exchange (fD) and alveolar size (Vs/Va) were significantly decreased in elastase-treated mice, and moderately correlated with the plethysmography parameters. Of importance, we could detect a decrease of the fD value in low-density areas with micro-CT, suggesting that gas exchange decreased in emphysematous lesions. Likewise, these parameters (fD and Vs/Va) were also decreased in adiponectin knockout mice, which exhibit emphysema with a homogeneous distribution. We demonstrated the feasibility of (129)Xe MRI and micro-CT in combination with traditional modalities. These noninvasive modalities provide complementary data that can be used for repeated estimations of regional gas exchange and lung morphology.

Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats.

Adiponectin is an adipocytokine that modulates energy homeostasis and glucose metabolism. Here, we examined the effects of acute intravenous (iv) and lateral cerebral ventricular (LCV) injections of adiponectin on the renal sympathetic nerve activity (RSNA) and blood pressure (b/p) in urethane-anesthetized rats. Both iv and LCV injections of adiponectin induced dose-dependent suppressions of RSNA and b/p. Moreover, we found that bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of iv injection of adiponectin on RSNA and b/p. These findings suggest that adiponectin decreases the RSNA and b/p in a dose-dependent manner and that the SCN is implicated in mechanism of adiponectin actions on RSNA and b/p. These findings also suggest that the hypotensive-action activity of adiponectin is realized, at least partially, via changes in activities of autonomic nerves activity.

Plasma adiponectin levels predict cardiovascular events in the observational Arita Cohort Study in Japan: the importance of the plasma adiponectin levels.

As the plasma level of adiponectin is related to metabolic syndrome and cardiovascular events, a low plasma adiponectin level may either cause or trigger cardiovascular disorders. The purpose of this study was to determine whether a low adiponectin level contributes to cardiovascular events, and to investigate the factors influencing adiponectin in the Japanese Arita-cho cohort study.We followed about 2000 subjects in Arita-cho, Saga, Japan as a cohort study, and we enrolled 637 subjects (205 men; 65.1±8.3 years old) who participated in annual health checks from 2005 to 2008 and underwent measurement of the plasma adiponectin level and an oral glucose tolerance test. We monitored the incidence of cardiovascular or cerebrovascular events in these subjects until the end of 2010, discontinuing follow-up at 3 years after the start of enrollment. Subjects with low plasma adiponectin levels (<10.5 ng ml(-1)) had a higher incidence of newly diagnosed cardiovascular diseases such as acute heart failure or acute myocardial infarction than those with high plasma adiponectin levels (≥10.5 ng ml(-1)) over an average of 2.95 years of follow-up. Multivariate analysis showed that the adiponectin level was predicted by the following parameters in all subjects: age (ß=0.16), male gender (ß=-0.267), homeostasis model assessment of insulin resistance (ß=-0.140) and the plasma levels of high-density lipoprotein cholesterol (ß=0.104), uric acid (ß=-0.13), triglycerides (ß=-0.169) and brain natriuretic peptide (ß=0.151). The difference in plasma glucose before and 120 min after the intake of a 75-g glucose load did not influence the plasma adiponectin level. The plasma adiponectin level is useful for predicting cardiovascular events, and is a measure of the risk of lifestyle-related diseases.