Spinophilin regulates central angiotensin II-mediated effect on blood pressure

• Published in: Journal of molecular medicine (Berlin, Germany) Germany), 2011-12, Vol.89 (12), p.1219-1229
• Main Authors: da Costa Goncalves, Andrey C., Fontes, Marco Antonio Peliky, Klussmann, Enno, Qadri, Fatimunnisa, Janke, Jürgen, Gollasch, Maik, Schleifenbaum, Johanna, Müller, Dominik, Jordan, Jens, Tank, Jens, Luft, Friedrich C., Gross, Volkmar
• Format: Article
• Language: English
• Subjects: Angiotensin II - physiology; Animals; Antidiuretic Hormone Receptor Antagonists; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood Pressure - physiology; Brain - metabolism; Gene Expression Regulation; General aspects; Heart Rate; Human Genetics; Internal Medicine; Male; Medical sciences; Mice; Mice, Knockout; Microfilament Proteins - physiology; Molecular Medicine; Nerve Tissue Proteins - physiology; Nitric Oxide Synthase Type I - genetics; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Original Article; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - genetics; Receptor, Angiotensin, Type 2 - metabolism; Receptors, Vasopressin - genetics; Receptors, Vasopressin - metabolism; Vasopressins - genetics; Vasopressins - metabolism
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-011-0793-8

Central angiotensin II (AngII) plays an important role in the regulation of the sympathetic nervous system. The underlining molecular mechanisms are largely unknown. Spinophilin (SPL) is a regulator of G protein-coupled receptor signaling. Deletion of SPL induces sympathetically mediated arterial hypertension in mice. We tested the hypothesis that SPL restrains blood pressure (BP) by regulating AngII activity. We equipped SPL −/− and SPL +/+ mice with telemetric devices and applied AngII (1.0 mg kg −1  day −1 , minipumps) or the AngII subtype 1 receptor (AT1-R) blocker valsartan (50 mg kg −1  day −1 , gavage). We assessed autonomic nervous system activity through intraperitoneal application of trimethaphan, metoprolol, and atropine. We also tested the effect of intracerebroventricular (icv) AngII on blood pressure in SPL −/− and in SPL +/+ mice. Chronic infusion of AngII upregulates SPL expression in the hypothalamus of SPL +/+ mice. Compared with SPL +/+ mice, SPL −/− mice showed a greater increase in daytime BP with AngII (19.2 ± 0.8 vs. 13.5 ± 1.6 mmHg, p