Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice
| Autor: | José M. López-Novoa, Barbara Oujo, Isabel Fuentes-Calvo, Peter ten Dijke, Adela S. Riolobos, Miguel Pericacho, Orlando Castellano, Fernando Pérez-Barriocanal, María González-Núñez, María A. Sevilla, Ignacio Cruz-González |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Central Nervous System
Activin receptor-like kinase 1 Time Factors Activin Receptors Type II Vasodilator Agents lcsh:Medicine Medicine (miscellaneous) Vasodilation Angiotensin-Converting Enzyme Inhibitors Haploinsufficiency Renin-Angiotensin System Catecholamines Immunology and Microbiology (miscellaneous) Vasoconstrictor Agents Receptor Arterial pressure Mice Knockout Angiotensin II Intracerebroventricular injection Animal model of human disease Cholinergic Neurons Circadian Rhythm Losartan Phenotype Hypertension medicine.symptom lcsh:RB1-214 medicine.drug Research Article medicine.medical_specialty Heterozygote Neuroscience (miscellaneous) Biology General Biochemistry Genetics and Molecular Biology Internal medicine Renin–angiotensin system lcsh:Pathology medicine Animals Genetic Predisposition to Disease Cholinergic neuron Antihypertensive Agents Dose-Response Relationship Drug lcsh:R Nitric oxide Atenolol Mice Inbred C57BL Endocrinology Vasoconstriction Sympathetic nervous system Activin Receptors Type I Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | Disease Models and Mechanisms, 8(11), 1427-1439 Disease Models & Mechanisms Disease Models & Mechanisms, Vol 8, Iss 11, Pp 1427-1439 (2015) |
| DOI: | 10.1242/dmm.019695 |
| Popis: | 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. Summary: Mice haploinsufficient for Alk1, a receptor for the TGF-β family, show hypertension, based on overactivation of the sympathetic nervous system and a reduction in the number of cholinergic neurons in the CNS. |
| Databáze: | OpenAIRE |
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