Role of PACAP in the relationship between cAMP and opioids in hypoxia-induced pial artery vasodilation

1997 ◽  
Vol 272 (3) ◽  
pp. H1350-H1358 ◽  
Author(s):  
M. J. Wilderman ◽  
W. M. Armstead
Keyword(s):  
Adenylate Cyclase ◽  
Statistical Tests ◽  
Severe Hypoxia ◽  
Methionine Enkephalin ◽  
Pial Artery ◽  
Pituitary Adenylate Cyclase ◽  
Alpha Level ◽  
Before And After ◽  
The Relationship

The opioids methionine enkephalin and leucine enkephalin contribute to hypoxic pial artery dilation in the newborn pig, and adenosine 3',5'-cyclic monophosphate (cAMP) analogs have been shown to elevate cerebrospinal fluid (CSF) opioid concentration. The present study was designed to investigate the contribution of cAMP to hypoxic dilation and to determine whether an endogenous activator of adenylate cyclase, pituitary adenylate cyclase-activating peptide (PACAP), could modulate the cAMP-induced release of opioids to contribute to hypoxic pial dilation in piglets equipped with closed cranial windows. An alpha level of P < 0.05 was considered significant in all statistical tests. Moderate and severe hypoxia (PO2 approximately 35 and 25 mmHg, respectively) induced pial artery dilation that was attenuated by the Rp diastereomer of 8-bromoadenosine 3',5'-cyclic monophosphothioate (Rp-8-BrcAMPS), a cAMP antagonist (24 +/- 1 and 36 +/- 2% vs. 21 +/- 1 and 30 +/- 1% for moderate hypoxia and 34 +/- 1 and 46 +/- 2% vs. 24 +/- 1 and 32 +/- 1% for severe hypoxia before and after Rp-8-BrcAMPS, respectively). These responses were associated with an increased CSF cAMP (1,046 +/- 25, 1,366 +/- 28, and 1,735 +/- 47 fmol/ml for control, moderate, and severe hypoxia, respectively). Hypoxic pial dilation was also accompanied by an increase in CSF methionine enkephalin (1,101 +/- 62, 3,283 +/- 119, and 3,835 +/- 129 pg/ml for control, moderate, and severe hypoxia, respectively). Hypoxic dilation additionally increased CSF PACAP (1,727 +/- 86, 2,268 +/- 157, and 7,980 +/- 238 pg/ml for control, moderate, and severe hypoxia, respectively). PACAP (10(-8) and 10(-6) M) elicited pial dilation that was associated with increased CSF cAMP and blunted by Rp-8-BrcAMPS. PACAP-induced dilation was also accompanied by increases in the opioid methionine enkephalin (1,059 +/- 23, 1,483 +/- 34, and 2,108 +/- 77 pg/ml for control and 10(-8) and 10(-6) M PACAP, respectively). These data show that cAMP contributes to hypoxic pial artery dilation. Hypoxia increases CSF PACAP, whereas PACAP elevates CSF opioid concentration. These data, therefore, suggest that PACAP modulates cAMP-induced opioid release, thereby contributing to hypoxic pial dilation.

scholarly journals Role of opioids in hypoxic pial artery dilation is stimulus duration dependent

1998 ◽  
Vol 275 (3) ◽  
pp. H861-H867 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Stimulus Duration ◽  
Exposure Period ◽  
Hypoxic Exposure ◽  
Relative Role ◽  
Moderate Hypoxia ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After

Because methionine enkephalin contributes to and dynorphin opposes dilation during a 10-min hypoxic exposure, opioids modulate pial artery dilation to this stimulus. However, such modulation may be dependent on the duration of hypoxia. The present study was designed to characterize the modulation of hypoxic pial dilation by opioids as a function of stimulus duration in newborn pigs equipped with a closed cranial window. Hypoxic dilation was decremented in both moderate and severe groups ([Formula: see text] ≈ 35 and 25 mmHg, respectively) during 20-min and 40-min exposure periods compared with the response during 5 or 10 min of stimulation (24 ± 1, 25 ± 1, 18 ± 1, and 14 ± 1% for 5, 10, 20, and 40 min of moderate hypoxia; means ± SE). Moderate and severe hypoxia had no effect on cerebral spinal fluid (CSF) methionine enkephalin or dynorphin concentration during a 5-min exposure period. During a 10-min exposure, however, both opioids were increased in CSF. During 20- and 40-min exposure periods, CSF dynorphin continued to increase, whereas methionine enkephalin steadily decreased (962 ± 18, 952 ± 21, 2,821 ± 15, 2,000 ± 81, and 1,726 ± 58 pg/ml methionine enkephalin for control, 5, 10, 20, and 40 min of moderate hypoxia, respectively). The μ-opioid (methionine enkephalin) antagonist β-funaltrexamine had no influence on dilation during the 5-min exposure, decremented the 10- and 20-min exposures, but had no effect on 40-min exposure hypoxic dilation. Whereas the κ-opioid (dynorphin) antagonist norbinaltorphimine similarly had no effect on a 5-min exposure dilation, it, in contrast, potentiated 10-, 20-, and 40-min exposure hypoxic dilations (23 ± 1 vs. 23 ± 1, 24 ± 1 vs. 32 ± 1, 16 ± 1 vs. 24 ± 2, and 13 ± 1 vs. 23 ± 3% for 5, 10, 20, and 40-min hypoxic dilation before and after norbinaltorphimine). These data show that opioids do not modulate hypoxic pial dilation during short but do so during longer exposure periods. Moreover, hypoxic pial dilation is diminished during longer exposure periods. Decremented hypoxic pial dilation during longer exposure periods results, at least in part, from decreased release of methionine enkephalin and accentuated release of dynorphin. These data suggest that the relative role of opioids in hypoxic pial dilation changes with the stimulus duration.

Ventilatory response to moderate and severe hypoxia in adult dogs: role of endorphins

1988 ◽  
Vol 65 (3) ◽  
pp. 1383-1388 ◽  
Author(s):  
J. I. Schaeffer ◽  
G. G. Haddad
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Severe Hypoxia ◽  
Moderate Hypoxia ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Before And After ◽  
The Relationship ◽  
Arterial Po2

To determine the role of opioids in modulating the ventilatory response to moderate or severe hypoxia, we studied ventilation in six chronically instrumented awake adult dogs during hypoxia before and after naloxone administration. Parenteral naloxone (200 micrograms/kg) significantly increased instantaneous minute ventilation (VT/TT) during severe hypoxia, (inspired O2 fraction = 0.07, arterial PO2 = 28-35 Torr); however, consistent effects during moderate hypoxia (inspired O2 fraction = 0.12, arterial PO2 = 40-47 Torr) could not be demonstrated. Parenteral naloxone increased O2 consumption (VO2) in severe hypoxia as well. Despite significant increases in ventilation post-naloxone during severe hypoxia, arterial blood gas tensions remained the same. Control studies revealed that neither saline nor naloxone produced a respiratory effect during normoxia; also the preservative vehicle of naloxone induced no change in ventilation during severe hypoxia. These data suggest that, in adult dogs, endorphins are released and act to restrain ventilation during severe hypoxia; the relationship between endorphin release and moderate hypoxia is less consistent. The observed increase in ventilation post-naloxone during severe hypoxia is accompanied by an increase in metabolic rate, explaining the isocapnic response.

Opioids contribute to hypoxia-induced pial artery dilation through activation of ATP-sensitive K+ channels

1995 ◽  
Vol 269 (3) ◽  
pp. H997-H1002 ◽  
Author(s):  
V. Shankar ◽  
W. M. Armstead
Keyword(s):  
Severe Hypoxia ◽  
Methionine Enkephalin ◽  
K Channels ◽  
Leucine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Window Technique ◽  
Before And After ◽  
Newborn Pigs ◽  
Arterial Po2

It has been previously observed that hypoxia increases cerebrospinal fluid (CSF) methionine enkephalin and leucine enkephalin levels, and these opioids contribute to hypoxia-induced pial artery vasodilation. The present study was designed to investigate whether the activation of ATP-sensitive K+ channels (KATP) mediates the contribution of opioids to the hypoxia-induced pial artery dilation. The closed-cranial window technique was used to measure pial diameter in newborn pigs. Glibenclamide (10(-6) M), a KATP inhibitor, attenuated the dilation resulting from moderate and severe hypoxia [23 +/- 1 and 33 +/- 2% vs. 7 +/- 1 and 18 +/- 2%, respectively, for moderate and severe hypoxia (arterial PO2 approximately 35 and 25 mmHg, respectively) in the absence vs. presence of glibenclamide]. In addition, glibenclamide attenuated the dilation produced by methionine enkephalin (10(-8) and 10(-6) M) (13 +/- 1 vs. 4 +/- 2% and 21 +/- 2 vs. 7 +/- 3%, respectively, for methionine enkephalin in the absence and presence of glibenclamide). Leucine enkephalin-induced dilation was similarly attenuated by glibenclamide. Cromakalim (10(-8) and 10(-6) M), a KATP agonist, produced dilation that was blocked by glibenclamide (12 +/- 1 and 25 +/- 1 vs. 3 +/- 1 and 5 +/- 1% before and after glibenclamide, respectively). These data show that activation of KATP contributes to methionine enkephalin- and leucine enkephalin-induced dilation. Furthermore, these observations suggest that opioids contribute to hypoxia-induced pial artery dilation via KATP activation.

scholarly journals Role of Endothelial Nitric Oxide Synthase in Hypoxia-Induced Pial Artery Dilation

1998 ◽  
Vol 18 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Michael J. Wilderman ◽  
William M. Armstead
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Endothelial No Synthase ◽  
Before And After ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent release of methionine enkephalin and leucine enkephalin in the newborn pig. In separate studies, these opioids also were observed to elicit NO-dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to investigate the role of the endothelial isoform of NO synthase in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. N-iminoethyl-l-ornithine (l-NIO) (10−6 mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited by hypoxia (Po2 ≈ 35 mm Hg) (24 ± 2 versus 24 ± 2% in the absence and presence of l-NIO, respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP, which also was unchanged in the presence of l-NIO (394 ± 19 and 776 ± 63 versus 323 ± 13 and 739 ± 25 fmol/mL for control and hypoxia in the absence and presence of l-NIO, respectively, n = 6). Additionally, hypoxic pial dilation was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of l-NIO (992 ± 73 and 2469 ± 197 versus 984 ± 18 and 2275 ± 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin–induced dilation was blocked by l-NIO (6 ± 1, 10 ± 1, and 16 ± 1 versus 1 ± 1, 1 ± 1, and 2 ± 1% for 10−10, 10−8, 10−6 mol/L methionine enkephalin, respectively, before and after l-NIO, n = 8). Substance P–induced pial dilation was blunted by l-NIO, whereas responses to sodium nitroprusside and N-methyl-d-aspartate were unchanged. These data indicate that endothelial NO synthase contributes to opioid-induced pial artery dilation but not hypoxia-induced dilation. Additionally, these data suggest that neuronally derived NO contributes to hypoxic pial dilation.

scholarly journals Role of Nitric Oxide, Cyclic Nucleotides, and the Activation of ATP-Sensitive K+ Channels in the Contribution of Adenosine to Hypoxia-Induced Pial Artery Dilation

1997 ◽  
Vol 17 (1) ◽  
pp. 100-108 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Cyclic Nucleotides ◽  
Severe Hypoxia ◽  
Similar Data ◽  
Adenosine Receptor Antagonist ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Synthase Inhibitor

Previously, it had been observed that nitric oxide (NO) contributes to hypoxia-induced pial artery dilation in the newborn pig. Additionally, it was also noted that activation of ATP-sensitive K+ channels (KATP) contribute to cGMP-mediated as well as to hypoxia-induced pial dilation. Although somewhat controversial, adenosine is also thought to contribute to hypoxic cerebrovasodilation. The present study was designed to investigate the role of NO, cyclic nucleotides, and activation of KATP channels in the elicitation of adenosine's vascular response and relate these mechanisms to the contribution of adenosine to hypoxia-induced pial artery dilation. The closed cranial window technique was used to measure pial diameter in newborn pigs. Hypoxia-induced artery dilation was attenuated during moderate (PaO2 ≈ 35 mm Hg) and severe hypoxia (PaO2 ≈ 25 mm Hg) by the adenosine receptor antagonist 8-phenyltheophylline (8-PT) (10–5 M) (26 ± 2 vs. 19 ± 2 and 34 ± 2 vs. 22 ± 2% for moderate and severe hypoxia in the absence vs. presence of 8-PT, respectively). This concentration of 8-PT blocked pial dilation in response to adenosine (8 ± 2, 16 ± 2, and 23 ± 2 vs. 2 ± 2, 4 ± 2, and 6 ± 2% for 10–8, 10–6, and 10–4 M adenosine before and after 8-PT, respectively). Similar data were also obtained using adenosine deaminase as a probe for the role of adenosine in hypoxic pial dilation. Adenosine-induced dilation was associated with increased CSF cGMP concentration (390 ± 11 and 811 ± 119 fmol/ml for control and 10–4 M adenosine, respectively). The NO synthase inhibitor, L-NNA, and the cGMP antagonist, Rp 8-bromo cGMPs, blunted adenosine-induced pial dilation (8 ± 1, 14 ± 1, and 20 ± 3 vs. 3 ± 1, 5 ± 1, and 8 ± 3% for 10–8, 10–6, and 10–4 M adenosine before and after L-NNA, respectively). Adenosine dilation was also blunted by glibenclamide, a KATP antagonist (9 ± 2, 14 ± 3, 21 ± 4 vs. 4 ± 1, 8 ± 2, and 11 ± 2% for 10–8, 10–6, and 10–4 M adenosine before and after glibenclamide, respectively). Finally, it was also observed that adenosine-induced dilation was associated with increased CSF cAMP concentration and the cAMP antagonist, Rp 8-bromo cAMPs, blunted adenosine pial dilation. These data show that adenosine contributes to hypoxic pial dilation. These data also show that NO, cGMP, cAMP, and activation of KATP channels all contribute to adenosine induced pial dilation. Finally, these data suggest that adenosine contributes to hypoxia-induced pial artery dilation via cAMP and activation of KATP channels by NO and cGMP.

scholarly journals Analyzing the Relationship between Personnel's Education and Psychological Competence on Quality of Service: The Mediation Role of Organization Commitment in Ministry of the Interior

2016 ◽  
Vol 10 (3) ◽  
pp. 117
Author(s):  
Omid Ahmadi ◽  
Abdolali Keshtegar ◽  
Mohammad Ghasemi
Keyword(s):  
Quality Of Service ◽  
Organizational Commitment ◽  
Structural Equation ◽  
Statistical Population ◽  
Alpha Level ◽  
Psychological Competence ◽  
Correlational Method ◽  
The Relationship

<p>The goal of the present paper is to analyze the effect of personnel's education and psychological competence on<br />quality of service. The mediation role of organizational competence in Ministry of the Interior is of<br />descriptive-correlational method. To do that, the standard questionnaire psychological competence by Spriters<br />(1995), personnel education and quality of service by Deher (2015) and organizational commitment by Alen and<br />Mier (1990) were used. The statistical population of the research includes all personnel of Ministry of the<br />Interior which are 1600 subjects. Based on Cochran's formula, 3100 subjects were selected randomly. In order to<br />analyze data the Pearson's correlation test and structural equation of data analysis were used by SPSS and AMOS<br />software. The findings of the research indicate that personnel's education has a positive effect on organizational<br />competence and quality of service (with Alpha level of 0.05). Moreover, the psychological competence is<br />positively affect the quality of service (with Alpha level of 0.05) and organizational commitment affect the<br />quality of service. Finally, it was revealed that the personnel training through organizational commitment affect<br />the quality of service. But, psychological competence does not affect the quality of service through<br />organizational commitment. Moreover, psychological competence does not affect the organizational commitment.<br />The significance levelof the model turned out to be more than the first type error (0.05). This shows that the<br />significant adaption of the estimated model with the present research model. Furthermore, the AGFI and GFI<br />indicators are more than the estimated value (0.9). These indicators show that the model has a capability in<br />estimating the ratio of each factor.</p>

scholarly journals The Underestimated Value of Internal Marketing: Impact on Employee Satisfaction and Customer Satisfaction through Organisational Restructure

2021 ◽  
Author(s):  
◽  
Monica Nicole Micek
Keyword(s):  
Customer Satisfaction ◽  
Customer Service ◽  
Employee Satisfaction ◽  
Internal Marketing ◽  
Technological Advances ◽  
Before And After ◽  
Working Together ◽  
Internal Procedures ◽  
The Relationship

<p>Internal Marketing, a long-debated concept amongst academics and practitioners, is suggested to be a competitive advantage to organisations that utilise its practices. Often dismissed as merely selling the marketing of a product or service to employees within an organisation, Internal Marketing encompasses a combination of the key elements of communication, training, and feedback in order to create motivated, customer-orientated employees. Through employees and managers working together towards a well communicated organisational cause of Internal Marketing, internal procedures can evolve to better service and satisfy customers.  Organisational restructures are an ongoing concern as technological advances, value-adding business process, and globalisation change the way that businesses run and operate. In order to save on costs of operations, employment, and office rental space, downsizing an organisation may initially present itself as a cost-saving practice. Often unconsidered are the front-line customer-facing employees and customers of an organisation. Employees may feel distraught and concerned about losing their job, or having to find a new job, which may affect customer service, and subsequently customers may face the brunt of the domino effect, either intentionally or unintentionally, due to employees’ emotional disconnection from the organisation.  This research is an exploratory study into Internal Marketing, specifically around an organisational restructure, to better understand its impact on employees and customers through different stages of a restructure. Through the use of online surveys, participants were asked to recall an organisational restructure they were involved in within the last five years. They were asked to report their perceptions of Internal Marketing, their own satisfaction with their job at the time, and their perceptions of Customer Satisfaction throughout different stages of the organisational restructure.  The analysis found that Internal Marketing does have a significant positive relationship with Employee Satisfaction both during and after an organisational restructure. Although no significant relationship was found between Employee Satisfaction and Customer Satisfaction at any stage of the restructure, there is a trend within the data suggesting that the relationship may be stronger before and after an organisational restructure.  Benefits and contribution of this research for academics include development of a conceptual model, as well as the benefits and effects of Internal Marketing, and extending the existing literature. For practitioners, benefits include insights into better understanding of the role of Internal Marketing. Specifically, the differences in perception of the practice between employees and managers, and why it is important to understand and address Employee Satisfaction and Customer Satisfaction during an organisational restructure.</p>

scholarly journals Lack of Change Information and End User Grumbling: Mediating Role of Fear of Unknown and Moderating Role of Emotional Regulation

2020 ◽  
Vol 13 (3) ◽  
pp. 1-15
Author(s):  
Rida Bangash ◽  
Kausar Fiaz Khawaja ◽  
Sumayya Chughtai
Keyword(s):  
Emotional Regulation ◽  
Statistical Tests ◽  
Self Regulation ◽  
Successful Implementation ◽  
End User ◽  
User Resistance ◽  
Mediating Role ◽  
The Relationship ◽  
Moderating Role

User resistance is a complex phenomenon and is considered a major constraint towards the successful implementation and usage of information technology. Hence, in order to investigate the factors that may lead to user resistance; the current study proposes and investigates the mediating role of fear of unknown between lack of change information and end-user grumbling, and the moderating role of emotional regulation between the relationship. Emotional self-regulation theory has been used as an overarching theory that explains the research model proposed and tested in the study. Using a Quantitative approach, the survey was conducted and data was collected from 334 users of FBR systems. With the help of SPSS and MACRO PROCESS, statistical tests were conducted and links were tested. Results revealed that all hypotheses were accepted. Along with these discussions, research implications and recommendations are also provided.

scholarly journals PENGARUH REVIU RKA-K/L OLEH APIP TERHADAP EFISIENSI ALOKASI ANGGARAN KEMENTERIAN AGAMA

2019 ◽  
Vol 1 (1) ◽  
pp. 12
Author(s):  
Edy Effendi ◽  
Muhammad Imron
Keyword(s):  
Linear Regression ◽  
Simple Linear Regression ◽  
Independent Variables ◽  
Dependent Variables ◽  
Before And After ◽  
The Impact ◽  
The Relationship ◽  
Positive Effect

Research on the role of the APIP review of the Ministry/agency Work Plan and Budget document to determine the impact on the efficiency of ministry/agency spending (case study at the Ministry of Religion). The method used in this study uses simple linear regression with dummy. The use of linear regression is used to examine the relationship between independent variables (certain types of expenditure) and dependent variables (total expenditure). Whereas, dummy is used to find out before and after the APIP review is done. Throughout the author's search, this research has never been done. Based on the results of linear regression obtained, the APIP review significantly had a positive effect on official travel expenditure and honorarium but did not significantly affect building spending and equipment. Abstrak   Penelitian atas peran reviu APIP atas dokumen Rencana Kerja dan Anggaran Kementerian Negara/Lembaga untuk mengetahui dampaknya terhadap efisiensi belanja kementerian/lembaga (studi kasus pada Kementerian Agama). Metode yang digunakan dalam penelitian ini menggunakan regresi linier sederhana dengan dummy. Penggunaan regresi liner digunakan untuk meneliti hubungan antara variable independen (jenis belanja tertentu) dan variable dependen (total belanja). Sedangkan, dummy digunakan untuk mengetahui sebelum dan setelah reviu APIP dilakukan. Sepanjang penelusuran penulis, penelitian ini belum pernah dilakukan. Berdasarkan hasil regresi linier diperoleh, reviu APIP signifikan berpengaruh positif terhadap  belanja perjalanan dinas dan honorarium tetapi tidak signifikan berbengaruh terhadap belanja gedung dan alat.

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