Chronic p38 mitogen-activated protein kinase inhibition improves vascular function and remodeling in angiotensin II-dependent hypertension.

INTRODUCTION: An excess of angiotensin II (Ang II) causes hypertension and vascular injury. Activation of mitogen-activated protein kinase p38 (p38-MAPK) plays a substantial role in Ang II-dependent organ damage. Recently, we showed that p38-MAPK activation regulates the pressor response to Ang II. This study evaluates the effect of chronic p38-MAPK inhibition in Ang II-dependent hypertension. MATERIALS AND METHODS: C57Bl/6J mice were infused with Ang II for 14 days and either treated with the p38-MAPK inhibitor BIRB796 (50 mg/kg/day) or the vehicle as the control. We assessed vascular function in the aorta and isolated perfused kidneys. RESULTS: Chronic p38-MAPK inhibition did not alter blood pressure at the baseline, but attenuated Ang II-induced hypertension significantly (baseline: 122 ± 2 versus 119 ± 4 mmHg; Ang II: 173 ± 3 versus 155 ± 3 mmHg; p < 0.001). In addition, BIRB796 treatment improved vascular remodeling by reducing the aortic media-to-lumen ratio and decreasing the expression of the membrane metalloproteinases (MMP) MMP-1 and MMP-9. Moreover, renal vascular dysfunction induced by chronic Ang II infusion was significantly ameliorated in the BIRP796-treated mice. Acute p38-MAPK inhibition also improved vascular function in the aorta and kidneys of Ang II-treated mice, highlighting the important role of p38-MAPK activation in the pathogenesis of vascular dysfunction. CONCLUSIONS: Our findings indicated there is an important role for p38-MAPK in regulating blood pressure and vascular injury, and highlighted its potential as a pharmaceutical target.

[The legitimacy of single and group housing of breeding sows]. / Untersuchungen zur Artgerechtigkeit der Einzel- und Gruppenhaltung von Zuchtsauen.

Current German law on animal rights requires protection and appropriate treatment of animals. However, information on breeding and raising swine is incomplete, and comparison studies of alternative housing systems are needed. Therefore, the effects of single and group housing of pregnant sows on piglet production was investigated in the 120-sow herd of the Institute for Animal Breeding and Husbandry of the University of Kiel. Reproductive traits, general health and behaviour studies were evaluated over one year. Type of housing system was found to have no effect on number of piglets born alive or dead or on days open. Daily gain was influenced. Daily gain of single-housed sows increased but without any difference in feed intake. General health was measured by nutritional condition, soiling, callosity, and injuries at time of evaluation. Single-housed sows had more calluses and were more soiled compared with group-housed sows. Injuries occurred more often in group housing, especially when new animals were integrated into the group. However, injuries were not serious. Animal behaviour was recorded on video during one pregnancy period of 60 sows. The housing system effected "sitting" and "lying" behaviour. Behaviour also is influenced by pregnancy in both housing systems. Equal incidences of abnormal behaviour, considered as sham-chewing, were found in both housing systems.