PT  - JOURNAL ARTICLE
AU  - González-Núñez, María
AU  - Riolobos, Adela S.
AU  - Castellano, Orlando
AU  - Fuentes-Calvo, Isabel
AU  - de los Ángeles Sevilla, María
AU  - Oujo, Bárbara
AU  - Pericacho, Miguel
AU  - Cruz-Gonzalez, Ignacio
AU  - Pérez-Barriocanal, Fernando
AU  - ten Dijke, Peter
AU  - López-Novoa, Jose M.
TI  - Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice
AID  - 10.1242/dmm.019695
DP  - 2015 Nov 01
TA  - Disease Models & Mechanisms
PG  - 1427--1439
VI  - 8
IP  - 11
4099  - http://dmm.biologists.org/content/8/11/1427.short
4100  - http://dmm.biologists.org/content/8/11/1427.full
SO  - Dis Models Mech2015 Nov 01; 8
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.