Challenging Varieties of Capitalism's Account of Business Interests: The New Social Market Initiative and German Employers' Quest for Liberalization, 2000-2014

Do employers in coordinated market economies (CME's) actively defend the non-liberal, market- constraining institutions upon which their strategic coordination and competitive success depends? This paper revisits the debate over firms' employer preferences with an in-depth examination of employers in Germany - a paradigmatic CME and crucial "test case" for Varieties of Capitalism. It is based on interviews with key officials and an in-depth examination of a large-scale campaign - the New Social Market Initiative or INMS - founded and funded by German metalworking employers to shape public opinion. The paper argues that German employers have a strong preference for liberalization: they have pushed hard for the liberalization of labor markets, the reduction of government expenditures, the expansion of market-oriented freedoms, and cuts to social protection, employment protection and benefit entitlements. I find no empirical support for the claim that the INSM is an attempt to appease discontented firms within employers' associations. On the contrary: for many employers, the Agenda 2010 reforms did not go far enough. Following the discrediting of the Anglo-American model in the financial crisis, far-reaching concessions by employees, and the unexpected revitalization of the German economy, employers have moderated their demands - but liberalization remains their default preference. This paper also addresses the role of ideas and the conditions under which employer campaigns can influence policy.Verteidigen Arbeitgeber in koordinierten Marktwirtschaften aktiv die nichtliberalen, marktbeschränkenden Institutionen, von denen ihre Möglichkeiten zur strategischen Koordination und ihr Erfolg im Wettbewerb abhängen? Mit einer umfassenden Untersuchung der Präferenzen von Arbeitgebern in Deutschland, das als typisches Beispiel einer koordinierten Marktwirtschaft und wegweisender "Testfall" für die Theorie über Spielarten des Kapitalismus gilt, greift dieses Discussion Paper die Debatte über die Präferenzen von Unternehmen in ihrer Eigenschaft als Arbeitgeber auf. Es basiert auf Interviews mit führenden Arbeitgeberfunktionären sowie einer detaillierten Untersuchung der Initiative Neue Soziale Marktwirtschaft (INSM): einer groß angelegten, von deutschen Metallarbeitgebern initiierten und finanzierten Kampagne zur öffentlichen Meinungsbildung. Der Beitrag belegt eine deutliche Präferenz deutscher Arbeitgeber für die Liberalisierung. Mit Nachdruck haben sie sich für eine Liberalisierung der Arbeitsmärkte, eine Senkung der Staatsausgaben und eine Ausweitung marktorientierter Gestaltungsfreiheiten ebenso eingesetzt wie für Einschnitte bei der sozialen Sicherung, dem Kündigungsschutz und den Versorgungsansprüchen. Die Behauptung, die INSM sei ein Versuch, unzufriedene Unternehmen innerhalb der Arbeitgeberverbände zu beschwichtigen, lässt sich durch die empirischen Befunde nicht stützen. Im Gegenteil: Vielen Arbeitgebern gingen die Reformen im Zuge der Agenda 2010 nicht weit genug. Zwar haben die deutschen Arbeitgeber nach der Diskreditierung des angloamerikanischen Modells während der Finanzkrise, weitreichenden Zugeständnissen seitens der Arbeitnehmer sowie der unerwarteten Wiederbelebung der deutschen Wirtschaft ihre Forderungen gemäßigt - doch bleibt ihre grundlegende Präferenz für die Liberalisierung bestehen. Dieser Beitrag befasst sich außerdem mit der Rolle von Ideen sowie den Bedingungen, unter denen Arbeitgeberkampagnen politische Maßnahmen beeinflussen können

The Renin-Angiotensin System and Cardiovascular Disease

Cardiovascular disease continues to be the leading cause of death and morbidity in America. The most pervasive cause of cardiovascular disease is high blood pressure (hypertension) which damages blood vessels and the heart leading to heart attacks, stroke and kidney failure. A leading cause of hypertension is the renin-angiotensin system (RAS). The active peptide hormone of the system, angiotensin II constricts blood vessels increasing resistance to blood flow by acting on a class of receptors known as the AT-1 subtype. This stresses the blood-pumping ability of the heart. It also promotes atherosclerosis, cardiac fibrosis (stiffening of the heart) and retention of fluid. It also acts in the brain to cause thirst, salt appetite and increased sympathetic nervous system activity which further stresses the heart and blood vessels. Several classes of drugs which either block formation of angiotensin II or block the AT-1 receptor have been developed to counteract the RAS. They are widely used clinically with good efficacy. However, hypertension continues to be a major health problem for many, and improved strategies for combating this disorder are needed. The discovery that other angiotensin peptides, e.g., angiotensin III, angiotensin IV and angiotensin (1-7), have activity on their own, and can be formed by specific enzymes, e.g., angiotensin-converting enzyme-2 (ACE-2), as well as the discovery of new receptors and binding proteins for angiotensin peptides, e.g., the AT-4 receptor, the mas oncogene protein and a novel angiotensin II / angiotensin III binding protein offer the potential for new therapeutic approaches to counteract hypertension

INHIBITION OF ANGIOTENSIN-CONVERTING ENZYME-2 (ACE-2) ACTIVITAND RADIOLIGAND BINDING OF A PUTATIVE ACE-2 INHIBITOR

Objective. This study was conducted to test the efficacy of novel ACE-2 inhibitor JFS101. Background. A potent inhibitor of ACE-2 (MLN-4760) was developed, but then abandoned when it became clear that ACE-2 metabolizes angiotensin II (Ang II) to form Ang 1-7. We developed a radioiodinizable analog of MLN-4760 (JFS101) that would more closely mimic Ang II. Methods. Both the uniodinated and monoradioiodinated as well as the S,S versus the S,R analogs were tested for their ability to inhibit ACE-2 metabolism of an artificial ACE-2 substrate (MCAAPK[ Dnp]) using recombinant human ACE-2 (rhACE-2) and for their ability to bind to ACE-2 in rat lung and kidney membranes. Results. The S,S isomer of JFS101 inhibited rhACE-2 in the nanomolar range and was 5-10% as potent as MLN-4760. The S,R isomer inhibited rhACE-2 activity in the low micromolar range. Radioligand binding assays using 125I-JFS101 (S,S isomer) revealed a high level of binding to lung and kidney membranes; however, less than 10% of this binding was displaceable by 1 μM MLN-4760. In contrast, 2 mM EDTA inhibited ~80% of total binding at 3-35 nM 125I-JFS101. Conclusion. The EDTA displaceable 125I-JFS101 binding was not saturable, suggesting that the KD of 125I-JFS101 for lung membranes is \u3e \u3e 35 nM. The inability of MLN-4760 combined with the ability of EDTA to inhibit 125I-JFS101 binding suggests that 125I-JFS101 is not selective for ACE-2, but that it does bind to another metallopeptidase. Grants. This study was funded by NIH-NHLBI HL113905

Renin-Angiotensin System Gene Expression and Neurodegenerative Diseases

Introduction: Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease. Materials and methods: A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis. Results: No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson’s disease and Alzheimer’s disease was also observed. Conclusions: To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases

Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer

OBJECTIVES: The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. MATERIALS AND METHODS: NCBI\u27s built-in statistical tool, GEO2R, was used to calculate Student\u27s RESULTS: Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT CONCLUSION: The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma

Searching for the Elusive Angiotensin-1-7 Receptor

Robert C. Speth, Ph.D. Professor, College of Pharmacy Filipe Stoyell-Conti, Research Associate, College of Pharmacy Alesa Chabbra, B.S. candidate, Halmos College of Natural Sciences and Oceanography Objective. To use radioligand binding assays to characterize the receptor(s) for angiotensin-1-7, a metabolite of the primary agonist of the renin-angiotensin system. Background. Angiotensin-1-7 (Ang- 1-7) was first reported to be a hormone in 1987. However, subsequent attempts to define its physiological function for this peptide were problematic. In 2003, we, Santos et al. reported that Ang-1-7 was an endogenous ligand for the protooncogene/orphan G protein-coupled receptor protein Mas. While we demonstrated 125I-Ang-1-7 binding using receptor autoradiography, it is necessary to demonstrate that this binding meets pharmacological criteria for a receptor. Methods. Classical radioligand binding assays of tissue membrane suspensions are incubated with a range of concentrations of 125/127I-Ang-1-7 or 3H-Ang-1-7 with and without non-radiolabeled Ang-1-7 or with different Ang peptides, e.g., AngII, AngIII, Ang-2-7, etc. “Specific” receptor binding of 125/127I-Ang-1-7 is evaluated using non-linear regression analysis to fit the Langmuir isotherm. Additionally, HPLC analysis of metabolism of Ang 1-7 in the assay is determined. Results. By varying assay medium constituents and peptidase inhibitors we can approximate the concentration and dissociation constant for 125/127I-Ang-1-7 binding in testis and liver of spontaneously hypertensive rats. However, other Ang peptides compete for this 125/127I-Ang-1-7 receptor equivalent to Ang-1-7, calling into question the pharmacological specificity of this binding site. Additionally, there is significant metabolism of Ang-1-7 which compromises the ability of the binding assays to obtain accurate values. Conclusion. We are continuing to validate this receptor binding assay to definitively characterize the receptor(s) for Ang-1-7. Grants. This study was partially funded by a PFRDG