Increased vascular α1-adrenergic receptor sensitivity in older adults with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is an independent risk factor for the development of hypertension and cardiovascular disease. Patients with PTSD have heightened blood pressure and sympathetic nervous system reactivity; however, it is unclear if patients with PTSD have exaggerated vasoconstriction in response to sympathetic nerve activation that could also contribute to increased blood pressure reactivity. Therefore, we hypothesized that patients with PTSD have increased sensitivity of vascular α1-adrenergic receptors (α1ARs), the major mediators of vasoconstriction in response to release of norepinephrine at sympathetic nerve terminals. To assess vascular α1AR sensitivity, we measured the degree of venoconstriction in a dorsal hand vein in response to exponentially increasing doses of the selective α1AR agonist, phenylephrine (PE), in 9 patients with PTSD (age = 59 ± 2 yr) and 10 age-matched controls (age = 60 ± 1 yr). Individual dose-response curves were generated to determine the dose of PE that induces 50% of maximal venoconstriction (i.e., PE ED50) reflective of vascular α1AR sensitivity. In support of our hypothesis, PE ED50 values were lower in PTSD compared with controls (245 ± 54 ng/min vs. 1,995 ± 459 ng/min, P = 0.012), indicating increased vascular α1AR sensitivity in PTSD. The PTSD group also had an increase in slope of rise in venoconstriction, indicative of an altered venoconstrictive reactivity to PE compared with controls (19.8% ± 1.2% vs. 15.1% ± 1.2%, P = 0.009). Heightened vascular α1AR sensitivity in PTSD may contribute to augmented vasoconstriction and blood pressure reactivity to sympathoexcitation and to increased cardiovascular disease risk in this patient population.

Normal dendrite growth in Drosophila motor neurons requires the AP-1 transcription factor.

During learning and memory formation, information flow through networks is regulated significantly through structural alterations in neurons. Dendrites, sites of signal integration, are key targets of activity-mediated modifications. Although local mechanisms of dendritic growth ensure synapse-specific changes, global mechanisms linking neural activity to nuclear gene expression may have profound influences on neural function. Fos, being an immediate-early gene, is ideally suited to be an initial transducer of neural activity, but a precise role for the AP-1 transcription factor in dendrite growth remains to be elucidated. Here we measure changes in the dendritic fields of identified Drosophila motor neurons in vivo and in primary culture to investigate the role of the immediate-early transcription factor AP-1 in regulating endogenous and activity-induced dendrite growth. Our data indicate that (a) increased neural excitability or depolarization stimulates dendrite growth, (b) AP-1 (a Fos, Jun hetero-dimer) is required for normal motor neuron dendritic growth during development and in response to activity induction, and (c) neuronal Fos protein levels are rapidly but transiently induced in motor neurons following neural activity. Taken together, these results show that AP-1 mediated transcription is important for dendrite growth, and that neural activity influences global dendritic growth through a gene-expression dependent mechanism gated by AP-1.