Different impacts of α-and β-blockers in neurogenic hypertension produced by brainstem lesions in rat

Wen Hsien Lu, Kai Sheng Hsieh, Pei-Jung Lu, Yi Shan Wu, Wen Yu Ho, Pei Wen Cheng, Chi Cheng Lai, Michael Hsiao, Ching Jiunn Tseng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND:: Bilateral lesions of nucleus tractus solitarii in rat result in acute hypertension, pulmonary edema, and death within hours. The hypertension results from excessive catecholamine release. Catecholamine can activate connexin43 to regulate cell death. There is no study investigating the cardiopulmonary impacts of different adrenergic blockers and apoptosis mechanism in rat model. METHODS:: The authors microinjected 6-hydroxydopamine into nucleus tractus solitarii of the rat (n = 8 per group) and evaluated the cardiopulmonary changes after treatment with different concentrations of α1-blockers, α2-blockers, β-blockers, and α-agonists. RESULTS:: In the rat model, the authors found that prazosin (0.15 mg/kg) treatment could preserve cardiac output and reverse neutrophil infiltrations in lungs and lead to prevent pulmonary hemorrhagic edema. The time-dependent increases in connexin43 and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells induced by 6-hydroxydopamine lesions were decreased after prazosin treatment (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells at 6 h: 64.01 ± 2.41% vs. 24.47 ± 3.10%; mean ± SD, P < 0.001, in heart, and 80.83 ± 2.52% vs. 2.60 ± 1.03%, P < 0.001, in lung). However, propranolol caused further compromise of the already impaired cardiac output with consequence of rapid death. Phenylephrine enhanced the phenotype in the link between connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells but not yohimbine. Connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were more decreased with prazosin (0.15 and 0.3 mg/kg) than that with prazosin (0.05 mg/kg) treatment. CONCLUSIONS:: α1-Receptors are the keystones of the phenotype. In some brainstem encephalitis and brain injury with nucleus tractus solitarii involvement, early α1-receptor blockade treatment may prevent acute death from tissue apoptosis. α-Blockers can also decrease cerebral perfusion pressure, and further studies are needed in translation to brain injury with increased intracranial pressure.

Original languageEnglish
Pages (from-to)1192-1204
Number of pages13
JournalAnesthesiology
Volume120
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Connexin 43
DNA Nucleotidylexotransferase
Prazosin
Brain Stem
Solitary Nucleus
Hypertension
Oxidopamine
Pulmonary Edema
Cardiac Output
Brain Injuries
Catecholamines
Cerebrovascular Circulation
Apoptosis
Phenotype
Lung
Adrenergic Antagonists
Yohimbine
Neutrophil Infiltration
Intracranial Pressure
Phenylephrine

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Lu, Wen Hsien ; Hsieh, Kai Sheng ; Lu, Pei-Jung ; Wu, Yi Shan ; Ho, Wen Yu ; Cheng, Pei Wen ; Lai, Chi Cheng ; Hsiao, Michael ; Tseng, Ching Jiunn. / Different impacts of α-and β-blockers in neurogenic hypertension produced by brainstem lesions in rat. In: Anesthesiology. 2014 ; Vol. 120, No. 5. pp. 1192-1204.
@article{b0f0495584e34ec2a404b61e73cec14a,
title = "Different impacts of α-and β-blockers in neurogenic hypertension produced by brainstem lesions in rat",
abstract = "BACKGROUND:: Bilateral lesions of nucleus tractus solitarii in rat result in acute hypertension, pulmonary edema, and death within hours. The hypertension results from excessive catecholamine release. Catecholamine can activate connexin43 to regulate cell death. There is no study investigating the cardiopulmonary impacts of different adrenergic blockers and apoptosis mechanism in rat model. METHODS:: The authors microinjected 6-hydroxydopamine into nucleus tractus solitarii of the rat (n = 8 per group) and evaluated the cardiopulmonary changes after treatment with different concentrations of α1-blockers, α2-blockers, β-blockers, and α-agonists. RESULTS:: In the rat model, the authors found that prazosin (0.15 mg/kg) treatment could preserve cardiac output and reverse neutrophil infiltrations in lungs and lead to prevent pulmonary hemorrhagic edema. The time-dependent increases in connexin43 and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells induced by 6-hydroxydopamine lesions were decreased after prazosin treatment (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells at 6 h: 64.01 ± 2.41{\%} vs. 24.47 ± 3.10{\%}; mean ± SD, P < 0.001, in heart, and 80.83 ± 2.52{\%} vs. 2.60 ± 1.03{\%}, P < 0.001, in lung). However, propranolol caused further compromise of the already impaired cardiac output with consequence of rapid death. Phenylephrine enhanced the phenotype in the link between connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells but not yohimbine. Connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were more decreased with prazosin (0.15 and 0.3 mg/kg) than that with prazosin (0.05 mg/kg) treatment. CONCLUSIONS:: α1-Receptors are the keystones of the phenotype. In some brainstem encephalitis and brain injury with nucleus tractus solitarii involvement, early α1-receptor blockade treatment may prevent acute death from tissue apoptosis. α-Blockers can also decrease cerebral perfusion pressure, and further studies are needed in translation to brain injury with increased intracranial pressure.",
author = "Lu, {Wen Hsien} and Hsieh, {Kai Sheng} and Pei-Jung Lu and Wu, {Yi Shan} and Ho, {Wen Yu} and Cheng, {Pei Wen} and Lai, {Chi Cheng} and Michael Hsiao and Tseng, {Ching Jiunn}",
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Lu, WH, Hsieh, KS, Lu, P-J, Wu, YS, Ho, WY, Cheng, PW, Lai, CC, Hsiao, M & Tseng, CJ 2014, 'Different impacts of α-and β-blockers in neurogenic hypertension produced by brainstem lesions in rat', Anesthesiology, vol. 120, no. 5, pp. 1192-1204. https://doi.org/10.1097/ALN.0000000000000218

Different impacts of α-and β-blockers in neurogenic hypertension produced by brainstem lesions in rat. / Lu, Wen Hsien; Hsieh, Kai Sheng; Lu, Pei-Jung; Wu, Yi Shan; Ho, Wen Yu; Cheng, Pei Wen; Lai, Chi Cheng; Hsiao, Michael; Tseng, Ching Jiunn.

In: Anesthesiology, Vol. 120, No. 5, 01.01.2014, p. 1192-1204.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Different impacts of α-and β-blockers in neurogenic hypertension produced by brainstem lesions in rat

AU - Lu, Wen Hsien

AU - Hsieh, Kai Sheng

AU - Lu, Pei-Jung

AU - Wu, Yi Shan

AU - Ho, Wen Yu

AU - Cheng, Pei Wen

AU - Lai, Chi Cheng

AU - Hsiao, Michael

AU - Tseng, Ching Jiunn

PY - 2014/1/1

Y1 - 2014/1/1

N2 - BACKGROUND:: Bilateral lesions of nucleus tractus solitarii in rat result in acute hypertension, pulmonary edema, and death within hours. The hypertension results from excessive catecholamine release. Catecholamine can activate connexin43 to regulate cell death. There is no study investigating the cardiopulmonary impacts of different adrenergic blockers and apoptosis mechanism in rat model. METHODS:: The authors microinjected 6-hydroxydopamine into nucleus tractus solitarii of the rat (n = 8 per group) and evaluated the cardiopulmonary changes after treatment with different concentrations of α1-blockers, α2-blockers, β-blockers, and α-agonists. RESULTS:: In the rat model, the authors found that prazosin (0.15 mg/kg) treatment could preserve cardiac output and reverse neutrophil infiltrations in lungs and lead to prevent pulmonary hemorrhagic edema. The time-dependent increases in connexin43 and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells induced by 6-hydroxydopamine lesions were decreased after prazosin treatment (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells at 6 h: 64.01 ± 2.41% vs. 24.47 ± 3.10%; mean ± SD, P < 0.001, in heart, and 80.83 ± 2.52% vs. 2.60 ± 1.03%, P < 0.001, in lung). However, propranolol caused further compromise of the already impaired cardiac output with consequence of rapid death. Phenylephrine enhanced the phenotype in the link between connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells but not yohimbine. Connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were more decreased with prazosin (0.15 and 0.3 mg/kg) than that with prazosin (0.05 mg/kg) treatment. CONCLUSIONS:: α1-Receptors are the keystones of the phenotype. In some brainstem encephalitis and brain injury with nucleus tractus solitarii involvement, early α1-receptor blockade treatment may prevent acute death from tissue apoptosis. α-Blockers can also decrease cerebral perfusion pressure, and further studies are needed in translation to brain injury with increased intracranial pressure.

AB - BACKGROUND:: Bilateral lesions of nucleus tractus solitarii in rat result in acute hypertension, pulmonary edema, and death within hours. The hypertension results from excessive catecholamine release. Catecholamine can activate connexin43 to regulate cell death. There is no study investigating the cardiopulmonary impacts of different adrenergic blockers and apoptosis mechanism in rat model. METHODS:: The authors microinjected 6-hydroxydopamine into nucleus tractus solitarii of the rat (n = 8 per group) and evaluated the cardiopulmonary changes after treatment with different concentrations of α1-blockers, α2-blockers, β-blockers, and α-agonists. RESULTS:: In the rat model, the authors found that prazosin (0.15 mg/kg) treatment could preserve cardiac output and reverse neutrophil infiltrations in lungs and lead to prevent pulmonary hemorrhagic edema. The time-dependent increases in connexin43 and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells induced by 6-hydroxydopamine lesions were decreased after prazosin treatment (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells at 6 h: 64.01 ± 2.41% vs. 24.47 ± 3.10%; mean ± SD, P < 0.001, in heart, and 80.83 ± 2.52% vs. 2.60 ± 1.03%, P < 0.001, in lung). However, propranolol caused further compromise of the already impaired cardiac output with consequence of rapid death. Phenylephrine enhanced the phenotype in the link between connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells but not yohimbine. Connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were more decreased with prazosin (0.15 and 0.3 mg/kg) than that with prazosin (0.05 mg/kg) treatment. CONCLUSIONS:: α1-Receptors are the keystones of the phenotype. In some brainstem encephalitis and brain injury with nucleus tractus solitarii involvement, early α1-receptor blockade treatment may prevent acute death from tissue apoptosis. α-Blockers can also decrease cerebral perfusion pressure, and further studies are needed in translation to brain injury with increased intracranial pressure.

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