OBJECTIVE The alpha 1-adrenoreceptor blocker doxazosin, which in the ALLHAT trial was associated with a greater risk of heart failure than the diuretic chlorthalidone, induces the apoptosis of human and murine cardiomyocytes regardless of alpha 1-adrenoreceptor blockade. We aimed to throw light on the mechanism of this process. METHODS Murine cardiomyocytes (HL-1) and primary cultures of huma...

Chronic opioid exposure induces neuroadaptative changes in several brain systems. Amongst others the alpha adrenergic system appears to be extremely sensitive to opioid exposure and has, therefore, been proposed to play a key role in opiate withdrawal symptoms. In order to better understand the influence of the noradrenergic system in opioid withdrawal and be able to develop new therapeutic str...

The calorigenic action of norepinephrine in isolated brown adipocytes was selectively mimicked by theophylline, dibutyryl cyclic AMP, and the principal fatty acids known to be present in the acyl moieties of brown adipose tissue triglycerides (palmitic, oleic, and linoleic acids). The stimulatory effects of fatty acids were entirely reversible, occurred at physiological concentrations, and were...

A new series of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide and 3,5,6,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-one derivatives were designed, synthesized, their binding and functional properties as α1-adrenoreceptors blockers were evaluated. A new validated α1-adrenoreceptor blocker pharmacophore model (hypothesis) was generated using Discovery Studio 2.5. The c...

-Adrenoreceptors Reactivate Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication via PKA-Dependent Control of Viral RTA Margaret Chang, Helen J. Brown, Alicia Collado-Hidalgo, Jesusa M. Arevalo, Zoran Galic, Tonia L. Symensma, Lena Tanaka, Hongyu Deng, Jerome A. Zack, Ren Sun, and Steve W. Cole* Departments of Microbiology, Immunology and Molecular Genetics, Molecular and Medical Pharmacol...

For those who have comfortably accepted the mechanistic link between sympathetic nervous system activation and poor outcome in heart failure, the study by Brede et al1 in this issue of Circulation is a welcome confirmation. The authors appear to have demonstrated in a murine model that absence of sympathoinhibitory 2 adrenoreceptors is associated with overactive catecholamine release, aggressiv...