Hypertension in beta-adducin-deficient mice

Polymorphic variants of the cytoskeletal protein adducin have been associat ed with hypertension in humans and rats. However, the direct role of this p rotein in modulating arterial blood pressure has never been demonstrated. T o assess the effect of beta-adducin on blood pressure, a beta-adducin-defic ient mouse strain (-/-) was studied and compared with wild-type controls (/+). Aortic blood pressure was measured in nonanesthetized, freely moving a nimals with the use of telemetry implants. It is important to note that the se mice have at least 98% of C57B1/6 genetic background, with the only diff erence from wild-type animals being the beta-adducin mutation. We found sta tistically significant higher levels of systolic blood pressure (mm Hg) (me an+/-SE values: -/-: 126.94+/-1.14, n=5; +/+: 108.06+/-2.34, n=6; P less th an or equal to 0.0001), diastolic blood pressure (-/-: 83.54+/-1.07; +/+: 7 4.87+/-2.23; P less than or equal to 0.005), and pulse blood pressure (-/-: 43.32+/-1.10; +/+: 33.19+/-1.96; P less than or equal to 0.001) in beta-ad ducin-deficient mice. Western blot analysis showed that as a result of the introduced genetic modification, beta-adducin was not present in heart prot ein extracts from -/- mice. Consequently, this deficiency produced a sharp decrease of alpha-adducin and a lesser reduction in gamma-adducin levels. H owever, we found neither cardiac remodeling nor modification of the heart f unction in these animals. This is the first report showing direct evidence that hypertension is triggered by a mutation in the adducin gene family.