RT Journal Article
SR Electronic
T1 Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice
JF Disease Models & Mechanisms
JO Dis Models Mech
FD The Company of Biologists Limited
SP 1427
OP 1439
DO 10.1242/dmm.019695
VO 8
IS 11
A1 González-Núñez, María
A1 Riolobos, Adela S.
A1 Castellano, Orlando
A1 Fuentes-Calvo, Isabel
A1 de los Ángeles Sevilla, María
A1 Oujo, Bárbara
A1 Pericacho, Miguel
A1 Cruz-Gonzalez, Ignacio
A1 Pérez-Barriocanal, Fernando
A1 ten Dijke, Peter
A1 López-Novoa, Jose M.
YR 2015
UL http://dmm.biologists.org/content/8/11/1427.abstract
AB The activin receptor-like kinase 1 (ALK-1) is a type I cell-surface receptor for the transforming growth factor-β (TGF-β) family of proteins. Hypertension is related to TGF-β1, because increased TGF-β1 expression is correlated with an elevation in arterial pressure (AP) and TGF-β expression is upregulated by the renin-angiotensin-aldosterone system. The purpose of this study was to assess the role of ALK-1 in regulation of AP using Alk1 haploinsufficient mice (Alk1+/−). We observed that systolic and diastolic AP were significantly higher in Alk1+/− than in Alk1+/+ mice, and all functional and structural cardiac parameters (echocardiography and electrocardiography) were similar in both groups. Alk1+/− mice showed alterations in the circadian rhythm of AP, with higher AP than Alk1+/+ mice during most of the light period. Higher AP in Alk1+/− mice is not a result of a reduction in the NO-dependent vasodilator response or of overactivation of the peripheral renin-angiotensin system. However, intracerebroventricular administration of losartan had a hypotensive effect in Alk1+/− and not in Alk1+/+ mice. Alk1+/− mice showed a greater hypotensive response to the β-adrenergic antagonist atenolol and higher concentrations of epinephrine and norepinephrine in plasma than Alk1+/+ mice. The number of brain cholinergic neurons in the anterior basal forebrain was reduced in Alk1+/− mice. Thus, we concluded that the ALK-1 receptor is involved in the control of AP, and the high AP of Alk1+/− mice is explained mainly by the sympathetic overactivation shown by these animals, which is probably related to the decreased number of cholinergic neurons.