In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 4 ( 2008-10), p. 702-707
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.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/HYPERTENSIONAHA.108.114355
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2008
detail.hit.zdb_id:
2094210-2
Permalink