Elastin mutation is associated with a reduced gain of the baroreceptor--heart rate reflex in patients with Williams syndrome.
Microdeletion of chromosome 7q, encompassing the elastin locus, has been identified in patients with Williams syndrome (WS). This study tested the hypothesis that loss of medial elastin affects the discharge of baroreceptors and consequently the baroreflex sensitivity (BRS). Eight untreated patients with WS (14.8 +/- 2.4 y, m +/- SEM) were compared to 8 healthy subjects (15.1 +/- 2.3 y). Blood pressure (BP) was recorded using a Finapres monitor in the supine position. Systolic BP (SBP) levels were 117.8 +/- 4.4 mmHg in WS compared to 110.9 +/- 5.7 in controls (ns). Pulse rate (PR, taken as a surrogate for heart rate) was higher in the WS (89.6 +/- 1.0 vs 74.1 +/- 2.3 beats/min in controls, P < 0.01). The variance (total power) of PI variability was reduced in WS subjects. The amplitudes of the low frequency (LF, 0.1 Hz) and high frequency (HF, respiratory) PI component (modulus) were reduced in WS (210.5 +/- 4.3 vs 34.6 +/- 2.6 ms, P = 0.02 for LF, for HF). The gain of the SBP-PI transfer function was diminished in the low frequency (LF, 0.1 Hz) and the HF range as well (5.8 +/- 0.7 vs 12.1 +/- 1.8 ms/mmHg for LF, P < 0.01 and 6.2 +/- 1.0 vs 21.7 +/- 4.6 ms/mmHg for HF, P < 0.01). The BRS obtained with the sequence technique was also reduced in WS (8.2 +/- 0.9 vs 21.5 +/- 2.9 ms/mm Hg in controls, P < 0.001). The percent of beats involved in baroreflex sequences observed in WS was also diminished to 20% compared to 48% in controls (P < 0.001). In conclusion a BRS reduction associated with a PR elevation was observed in normotensive WS subjects. It is likely abnormal elastic fiber assembly at the arterial level alters baroreceptor discharges.
Girard
Arlette
A
Départment de Néphrologie, Hôpital Necker, Paris, France.
Sidi
Daniel
D
Aggoun
Yacine
Y
Laude
Dominique
D
Bonnet
Damien
D
Elghozi
Jean-Luc
JL
D000293:Adolescent; D017704:Baroreflex / Q000235:genetics*; D004549:Elastin / Q000235:genetics*; D005260:Female; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D018980:Williams Syndrome / Q000235:genetics* / Q000503:physiopathology
D004549:Elastin