| First Author | González-Núñez M | Year | 2015 |
| Journal | Dis Model Mech | Volume | 8 |
| Issue | 11 | Pages | 1427-39 |
| PubMed ID | 26398936 | Mgi Jnum | J:226550 |
| Mgi Id | MGI:5697750 | Doi | 10.1242/dmm.019695 |
| Citation | Gonzalez-Nunez M, et al. (2015) Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice. Dis Model Mech 8(11):1427-39 |
| abstractText | The activin receptor-like kinase 1 (ALK-1) is a type I cell-surface receptor for the transforming growth factor-beta (TGF-beta) family of proteins. Hypertension is related to TGF-beta1, because increased TGF-beta1 expression is correlated with an elevation in arterial pressure (AP) and TGF-beta 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 beta-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. |
