BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II
| Autor: | Chris L. Schaich, Blanka Koi, Theresa L. Wellman, Benedek Erdos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Sympathetic Nervous System Angiotensin-Converting Enzyme Inhibitors Blood Pressure Tropomyosin receptor kinase B 030204 cardiovascular system & hematology Cardiovascular System Article Receptor Angiotensin Type 1 Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Internal medicine Renin–angiotensin system medicine Animals Vasoconstrictor Agents Brain-derived neurotrophic factor biology Endocrine and Autonomic Systems business.industry Angiotensin II Brain-Derived Neurotrophic Factor digestive oral and skin physiology Angiotensin-converting enzyme Endocrinology Losartan nervous system chemistry Hypothalamus Hypertension biology.protein Hexamethonium Neurology (clinical) business Angiotensin II Type 1 Receptor Blockers hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug Paraventricular Hypothalamic Nucleus |
| Zdroj: | Auton Neurosci |
| Popis: | Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during hypertensive stimuli including stress and hyperosmolarity, but its role in PVN cardiovascular regulatory mechanisms is unclear. Chronic BDNF overexpression in the PVN has been shown to elevate sympathetic tone and blood pressure in part by modulating central angiotensin (Ang) II mechanisms. However, the cardiovascular effects of short-term increases in PVN levels of BDNF and the mechanisms governing them are unknown. Therefore, we investigated whether acute BDNF microinjections into the PVN of conscious and anesthetized Sprague-Dawley rats induce blood pressure elevations and whether Ang II signaling is involved in these hypertensive responses. In conscious rats, unilateral BDNF (12.5 ng) microinjections into the PVN increased mean arterial pressure (MAP) by 27 ± 1 mm Hg (P < 0.001 vs vehicle), which was significantly attenuated by intracerebroventricular infusion of the Ang II-type-1 receptor (AT(1)R) antagonist losartan and by ganglionic blockade with intravenous hexamethonium infusion. In anesthetized rats, unilateral PVN microinjection of BDNF increased MAP by 31 ± 4 mm Hg (P < 0.001 vs vehicle), which was prevented by PVN microinjection pretreatments with the high-affinity BDNF receptor TrkB antagonist ANA-12, losartan, the angiotensin converting enzyme inhibitor lisinopril, or by intravenous hexamethonium. Additional experiments in hypothalamic samples including the PVN revealed that BDNF-induced TrkB receptor phosphorylation was prevented by ANA-12 and losartan pretreatments. Collectively, these data indicate that BDNF acting within the PVN acutely raises blood pressure under permissive control of Ang II-AT(1)R mechanisms and therefore may play an important role in mediating acute pressor responses to hypertensive stimuli. |
| Databáze: | OpenAIRE |
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