Delayed arteriolar relaxation after prolonged agonist exposure: functional remodeling involving tyrosine phosphorylation

2003 ◽  
Vol 285 (2) ◽  
pp. H849-H856 ◽  
Author(s):  
Michael A. Hill ◽  
Simon J. Potocnik ◽  
Luis A. Martinez-Lemus ◽  
Gerald A. Meininger

Although arteriolar contraction is dependent on Ca2+-induced myosin phosphorylation, other mechanisms including Ca2+ sensitization and time-dependent phenomena such as cytoskeletal and cellular reorganization may contribute to contractile events. We hypothesized that if arteriolar smooth muscle exhibits time-dependent behavior this may be manifested in differences in relaxation after short- and long-term exposure to contractile agonists. Studies were conducted in isolated arterioles pressurized to 70 mmHg. In initial experiments ( n = 10), rate of relaxation was measured after acute (5 min) or prolonged (4 h) exposure to 5 μM norepinephrine (NE). Prolonged exposure to NE resulted in significantly ( P < 0.05) increased time for relaxation in physiological salt solution. Rapid relaxation of vessels exposed to NE for 4 h was observed after superfusion with 0 mM Ca2+ buffer, indicating that the alteration in relaxation was reversible and Ca2+ dependent. A similarly impaired dilation was not observed with 4-h exposure to KCl (75 mM). To determine mechanisms contributing to the effects of prolonged NE exposure, studies were performed in the presence of the microtubule depolymerizing agent demecolcine (10 μM) or a series of tyrosine phosphorylation inhibitors. Although demecolcine caused significant vasoconstriction ( P < 0.05) and potentiated NE vasoconstriction, it did not prevent the effect of long-term NE exposure on relaxation. Genistein, although having no effect on acute NE-induced contraction, concentration-dependently inhibited prolonged NE constriction. Similarly, Src (PP1) and p42/44 MAP kinase (PD-98059) inhibitors prevented maintenance of long-term NE contraction. The data indicate that prolonged exposure to NE induces biochemical alterations that impair relaxation after removal of the agonist. The contractile effects are Ca2+ dependent and involve tyrosine phosphorylation but do not appear to involve the polymerization state of the microtubule network.

1997 ◽  
Vol 78 (6) ◽  
pp. 3460-3464 ◽  
Author(s):  
Terry Crow ◽  
Vilma Siddiqi

Crow, Terry and Vilma Siddiqi. Time-dependent changes in excitability after one-trial conditioning of Hermissenda. J. Neurophysiol. 78: 3460–3464, 1997. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. A one-trial conditioning procedure consisting of light paired with the application of serotonin (5-HT) to the exposed, but otherwise intact, nervous system produces suppression of phototactic behavior tested 24 h after conditioning. Short- and long-term enhancement (STE and LTE) of excitability in identified type B photoreceptors is a cellular correlate of one-trial conditioning. LTE can be expressed in the absence of STE suggesting that STE and LTE may be parallel processes. To examine the development of enhancement, we studied its time-dependent alterations after one-trial conditioning. Intracellular recordings from identified type B photoreceptors of independent groups collected at different times after conditioning revealed that enhanced excitability follows a biphasic pattern in its development. The analysis of spikes elicited by 2 and 30 s extrinsic current pulses at different levels of depolarization showed that enhancement reached a peak 3 h after conditioning. From its peak, excitability decreased toward baseline control levels 5–6 h after conditioning followed by an increase to a stable plateau at 16 to 24 h postconditioning. Excitability changes measured in cells from unpaired control groups showed maximal changes 1 h posttreatment that rapidly decremented within 2 h. The conditioned stimulus (CS) elicited significantly more spikes 24 h postconditioning for the conditioned group as compared with the unpaired control group. The analysis of the time-dependent development of enhancement may reveal the processes underlying different stages of memory for this associative experience.


2018 ◽  
Vol 56 (4) ◽  
pp. 669-680 ◽  
Author(s):  
Seline Zurfluh ◽  
Manuela Nickler ◽  
Manuel Ottiger ◽  
Christian Steuer ◽  
Alexander Kutz ◽  
...  

Abstract Background: The release of hormones from the adrenal gland is vital in acute and chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving recurrent exacerbations. Using a metabolomic approach, we aim to investigate associations of different adrenal hormone metabolites with short- and long-term mortality in COPD patients. Methods: We prospectively followed 172 COPD patients (median age 75 years, 62% male) from a previous Swiss multicenter trial. At baseline, we measured levels of a comprehensive spectrum of adrenal hormone metabolites, including glucocorticoid, mineralocorticoid and androgen hormones by liquid chromatography coupled with tandem mass spectrometry (MS). We calculated Cox regression models adjusted for gender, age, comorbidities and previous corticosteroid therapy. Results: Mortality was 6.4% after 30 days and increased to 61.6% after 6 years. Higher initial androgen hormones predicted lower long-term mortality with significant results for dehydroepiandrosterone (DHEA) [adjusted hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70–0.98; p=0.026] and dehydroepiandrosterone sulfate (DHEA-S) (adjusted HR, 0.68; 95% CI, 0.50–0.91; p=0.009). An activation of stress hormones (particularly cortisol and cortisone) showed a time-dependent effect with higher levels pointing towards higher mortality at short term, but lower mortality at long term. Activation of the mineralocorticoid axis tended to be associated with increased short-term mortality (adjusted HR of aldosterone, 2.76; 95% CI, 0.79–9.65; p=0.111). Conclusions: Independent of age, gender, corticosteroid exposure and exacerbation type, adrenal hormones are associated with mortality at short and long term in patients with COPD exacerbation with different time-dependent effects of glucocorticoids, androgens and mineralocorticoids. A better physiopathological understanding of the causality of these effects may have therapeutic implications.


2004 ◽  
Vol 41 (4) ◽  
pp. 644-656 ◽  
Author(s):  
Sangseom Jeong ◽  
Donghee Seo ◽  
Jinhyung Lee ◽  
Joogbai Park

A series of centrifuge model tests were performed to investigate the behavior of pile groups subjected to lateral soil movements by surcharge loading from approach embankments. The emphasis was on quantifying the time-dependent response in terms of deflections, bending moments, and earth pressures acting on pile groups during embankment construction and over short- and long-term periods after embankment construction. A variety of instruments were used to examine the soil–pile interaction for pile groups adjacent to surcharge loads. Through these studies, it is found that pile cap deflections and bending moments developed to their maximum values under the short-term surcharge loading and decreased gradually to minimum values under the long-term loading. The ground settlement reached its maximum value under long-term loading, however, due to the consolidation of soft clay. It is also found that the lateral mean pressure acting on the pile is about 0.75 and 0.35 times the surcharge load q (= γH, where γ is the unit weight of the soil and H is the height of the embankment) under short- and long-term loading, respectively.Key words: time-dependent response, lateral soil movements, pile groups, centrifuge model tests, surcharge loads, soft clay.


2017 ◽  
Vol 25 (7) ◽  
pp. 600-610 ◽  
Author(s):  
Hossein Sepiani ◽  
Maria Anna Polak ◽  
Alexander Penlidis

2001 ◽  
Vol 85 (2) ◽  
pp. 122-134 ◽  
Author(s):  
Alberto Sorace ◽  
Luigi De Acetis ◽  
Enrico Alleva ◽  
Daniela Santucci

Nature ◽  
1992 ◽  
Vol 357 (6373) ◽  
pp. 33-37 ◽  
Author(s):  
Susan Solomon ◽  
Daniel L. Albritton

2017 ◽  
Vol 117 ◽  
pp. 102-114 ◽  
Author(s):  
Patrícia Oliveira ◽  
Ângela Almeida ◽  
Vânia Calisto ◽  
Valdemar I. Esteves ◽  
Rudolf J. Schneider ◽  
...  

Author(s):  
Hame Park ◽  
Christoph Kayser

ABSTRACTOur senses often receive conflicting multisensory information, which our brain reconciles by adaptive recalibration. A classic example is the ventriloquist aftereffect, which emerges following both long-term and trial-wise exposure to spatially discrepant multisensory stimuli. Still, it remains debated whether the behavioral biases observed following short- and long-term exposure arise from largely the same or rather distinct neural origins, and hence reflect the same or distinct mechanisms. We address this question by probing EEG recordings for physiological processes predictive of the single-trial ventriloquism biases following the exposure to spatially offset audio-visual stimuli. Our results support the hypothesis that both short- and long-term aftereffects are mediated by common neurophysiological correlates, which likely arise from sensory and parietal regions involved in multisensory inference and memory, while prolonged exposure to consistent discrepancies additionally recruits prefrontal regions. These results posit a central role of parietal regions in mediating multisensory spatial recalibration and suggest that frontal regions contribute to increasing the behavioral bias when the perceived sensory discrepancy is consistent and persistent over time.


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