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Role of the multidomain protein spinophilin in blood pressure and cardiac function regulation

Item Type:Article
Title:Role of the multidomain protein spinophilin in blood pressure and cardiac function regulation
Creators Name:da Costa-Goncalves, A.C. and Tank, J. and Plehm, R. and Diedrich, A. and Todiras, M. and Gollasch, M. and Heuser, A. and Wellner, M. and Bader, M. and Jordan, J. and Luft, F.C. and Gross, V.
Abstract:Spinophilin controls intensity/duration of G protein-coupled receptor signaling and thereby influences synaptic activity. We hypothesize that spinophilin affects blood pressure through central mechanisms. We measured blood pressure and heart rate in SPL-deficient (SPL(-/-)), heterozygous SPL-deficient (SPL(+/-)), and wild-type (SPL(+/+)) mice by telemetry combined with fast Fourier transformation. We also assessed peripheral vascular reactivity and performed echocardiography. SPL(-/-) had higher mean arterial pressure than SPL(+/-) and SPL(+/+) (121+/-2, 112+/-1, and 113+/-1 mm Hg). Heart rate was inversely related to spinophilin expression (SPL(-/-) 565+/-0.4, SPL(+/-) 541+/-5, SPL(+/+) 525+/-8 bpm). The blood pressure response to prazosin, trimethapane, and the heart rate response to metoprolol were stronger in SPL(-/-) than SPL(+/+) mice, whereas heart rate response to atropine was attenuated in SPL(-/-). Mesenteric artery vasoreactivity after angiotensin II, phenylephrine, and the thromboxane mimetic (U46619) as well as change in heart rate, stroke volume, and cardiac output after dobutamine were similar in SPL(-/-) and SPL(+/+). Baroreflex sensitivity was attenuated in SPL(-/-) compared with SPL(+/-) and SPL(+/+), which was confirmed by pharmacological testing. Heart rate variability parameters were attenuated in SPL(-/-) mice. We suggest that an increase in central sympathetic outflow participates in blood pressure and heart rate increases in SPL(-/-) mice. The elevated blood pressure in SPL(-/-) mice was associated with attenuated baroreflex sensitivity and decreased parasympathetic activity. Our study is the first to show a role for the spinophilin gene in blood pressure regulation.
Keywords:Autonomic Nervous System, Blood Pressure Regulation, Spectral Analysis, Spinophilin-Deficient Mice, Telemetry, Animals, Mice
Publisher:American Heart Association
Page Range:702-707
Date:October 2008
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.108.114355
PubMed:View item in PubMed

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