| First Author | da Costa-Goncalves AC | Year | 2008 |
| Journal | Hypertension | Volume | 52 |
| Issue | 4 | Pages | 702-7 |
| PubMed ID | 18711009 | Mgi Jnum | J:154723 |
| Mgi Id | MGI:4397774 | Doi | 10.1161/HYPERTENSIONAHA.108.114355 |
| Citation | da Costa-Goncalves AC, et al. (2008) Role of the multidomain protein spinophilin in blood pressure and cardiac function regulation. Hypertension 52(4):702-7 |
| abstractText | 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. |
