Autonomic cardiovascular control in methyl-CpG-binding protein 2 (Mecp2) deficient mice.
Methyl-CpG-binding protein 2 is a transcription factor that is involved in gene silencing. It is mutated in the majority of cases of Rett syndrome. This X-linked neurodevelopmental disorder is reported to involve abnormalities in autonomic cardiovascular regulation. As an initial step in understanding the basis for these abnormalities we have characterized autonomic cardiovascular function in Mecp2 deficient mice. Arterial pressure waves were recorded in freely moving animals using telemetry. Baseline blood pressure and pulse interval (PI) as well as indices of heart rate variability (HRV): standard deviation of PI (SDNN), range encompassing 90% of PIs (PI90) and standard deviation of adjacent PIs (SDSD) were similar in Mecp2(+/+) and Mecp2(+/-) animals. Spectral analysis of mean arterial pressure (MAP) and PI in the frequency domain showed similar relative power in low frequency 1 (LF1, 08-0.4 Hz), low frequency 2 (LF2, 0.4-1.0 Hz), middle frequency (MF, 1-3 Hz) and high frequency (HF, 3.0-10.0 Hz) bands. Autonomic blockade with atropine or propranolol as well as elevation in ambient temperature to 32 degrees C resulted in changes in blood pressure, PI and HRV that did not differ between the strains. Atropine, propranolol and elevated temperature resulted in similar changes in both MAP and PI spectral power. Baroreceptor function was tested using intravenous injections of nitroprusside followed by phenylephrine. Maximum gain was not different. These results do reveal any disturbance of autonomic cardiovascular regulation in the Mecp2 deficient mouse genotype.
Bissonnette
John M
JM
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. bissonne@ohsu.edu
Knopp
Sharon J
SJ
Maylie
James
J
Thong
Tran
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000235:genetics; D001831:Body Temperature / Q000502:physiology; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006321:Heart / Q000294:innervation / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006979:Hyperthermia, Induced; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015518:Rett Syndrome / Q000150:complications / Q000201:enzymology / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D018680:Cholinergic Antagonists; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2