مورد إلكتروني
Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity.
| العنوان: | Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity. |
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| المؤلفون: | Liu, Kun |
| المصدر: | JCI insight; vol 3, iss 9, 98694; 2379-3708 |
| بيانات النشر: | eScholarship, University of California 2018-05-01 |
| تفاصيل مُضافة: | Liu, Kun Li, Dan Hao, Guoliang McCaffary, David Neely, Oliver Woodward, Lavinia Ioannides, Demetris Lu, Chieh-Ju Brescia, Marcella Zaccolo, Manuela Tandri, Harikrishna Ajijola, Olujimi A Ardell, Jeffrey L Shivkumar, Kalyanam Paterson, David J |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Elevated levels of brain natriuretic peptide (BNP) are regarded as an early compensatory response to cardiac myocyte hypertrophy, although exogenously administered BNP shows poor clinical efficacy in heart failure and hypertension. We tested whether phosphodiesterase 2A (PDE2A), which regulates the action of BNP-activated cyclic guanosine monophosphate (cGMP), was directly involved in modulating Ca2+ handling from stellate ganglia (SG) neurons and cardiac norepinephrine (NE) release in rats and humans with an enhanced sympathetic phenotype. SG were also isolated from patients with sympathetic hyperactivity and healthy donor patients. PDE2A activity of the SG was greater in both spontaneously hypertensive rats (SHRs) and patients compared with their respective controls, whereas PDE2A mRNA was only high in SHR SG. BNP significantly reduced the magnitude of the calcium transients and ICaN in normal Wistar Kyoto (WKY) SG neurons, but not in the SHRs. cGMP levels stimulated by BNP were also attenuated in SHR SG neurons. Overexpression of PDE2A in WKY neurons recapitulated the calcium phenotype seen in SHR neurons. Functionally, BNP significantly reduced [3H]-NE release in the WKY rats, but not in the SHRs. Blockade of overexpressed PDE2A with Bay 60-7550 or overexpression of catalytically inactive PDE2A reestablished the modulatory action of BNP in SHR SG neurons. This suggests that PDE2A may be a key target in modulating the action of BNP to reduce sympathetic hyperactivity. |
| مصطلحات الفهرس: | Heart, Stellate Ganglion, Neurons, Animals, Rats, Inbred SHR, Inbred WKY, Humans, Autonomic Nervous System Diseases, Calcium, Norepinephrine, Natriuretic Peptide, Brain, RNA, Messenger, Cyclic GMP, Case-Control Studies, Synaptic Transmission, Ventricular Function, Electromagnetic Fields, Adult, Aged, Middle Aged, Female, Male, Arrhythmias, Cardiac, Cyclic Nucleotide Phosphodiesterases, Type 2, Young Adult, Cardiology, Neuroscience, Phosphodiesterases, Cardiovascular, Hypertension, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf JCI insight vol 3, iss 9, 98694 2379-3708 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt05k459hj qt05k459hj https://escholarship.org/uc/item/05k459hj https://escholarship.org/ 1391610646 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1391610646 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |