1 mN and mechanoreceptor excitability in response to electrical stimulation were increased in TNBS-treated tissue, suggesting increased

sensitivity of the mechanotransducer. Mechanoreceptor function at 30 days posttreatment was in most cases unchanged. The inflammatory mediator prostaglandin E-2 (1 mu M) activated mechanoreceptors (6 days) in conjunction with contractile activity, but capsaicin (1 mu M) failed to activate mechanoreceptors. Stattic Bradykinin (1 mu M) activated mechanoreceptors independently of contractile activity and responses to stretch were increased in the presence of bradykinin. Both capsaicin and bradykinin activated unidentified stretch-insensitive afferents independently of contractile activity. Mechanoreceptor function is modulated at 6 days posttreatment but not at 30 days, suggesting a moderate increase in mechanoreceptor sensitivity in inflamed tissue but not after recovery. Other unclassified stretch-insensitive afferents are responsive to inflammatory mediators and capsaicin and may be involved in aspects of visceral sensation.”
“Primary aldosteronism is considered

to be responsible for almost 10% of all cases of arterial hypertension. The genetic background of this common disease, however, has been elucidated only for the rare familial types, whereas in the large majority of sporadic cases, underlying mechanisms still remain unclear. In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism, a mutagenesis screen after treatment of mice with the alkylating agent N-ethyl-N-nitrosourea was established for HIF inhibitor the parameter aldosterone. As the detection method we used a time-resolved fluorescence immunoassay that allows the measurement of aldosterone in very small murine sample volumes. Based on

this assay, we first determined the normal aldosterone values for wild-type C3HeB/FeJ mice under baseline conditions [92 +/- 6 pg/ml for females (n = 69) and 173 +/- 16 pg/ml for males (n = 55)]. Subsequently, aldosterone measurement was carried out in more than 2800 F(1) offspring of chemically mutagenized C3HeB/FeJ mice, and values were compared with aldosterone levels from untreated animals. Persistent hyperaldosteronism (defined as levels +3 SD above AZD1208 inhibitor the mean of untreated animals) upon repeated measurements was present in seven female and two male F(1) offspring. Further breeding of these founders gave rise to F(2) pedigrees from which eight lines with different patterns of inheritance of hyperaldosteronism could be established. These animals will serve for detailed phenotypic and genetic characterization in the future. Taken together, our data demonstrate the feasibility of a phenotype-driven mutagenesis screen to detect and establish mutant mouse lines with a phenotype of chronic hyperaldosteronism.