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Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
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Ebselen reduces cigarette smoke-induced endothelial dysfunction in mice.

Kurt Brassington1, Stanley M H Chan1, Huei Jiunn Seow1

  • 1School of Health & Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.

British Journal of Pharmacology
|February 1, 2021
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Cigarette smoke exposure damages blood vessels and lung inflammation in mice. The antioxidant ebselen protected against this vascular dysfunction by reducing oxidative stress and preserving eNOS expression.

Keywords:
antioxidantcardiovascular diseasechronic obstructive pulmonary diseasecigarette smokeendotheliumlung inflammationvascular dysfunction

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Area of Science:

  • Cardiovascular Research
  • Pulmonary Medicine
  • Pharmacology

Background:

  • Smokers and COPD patients have increased cardiovascular disease (CVD) risk.
  • Mechanisms linking COPD and CVD are not fully understood.
  • Oxidative stress is a known factor in COPD pathology.

Purpose of the Study:

  • Investigate if cigarette smoke (CS) impairs vascular function in mice.
  • Determine if the antioxidant ebselen prevents CS-induced vascular dysfunction.
  • Explore the role of oxidative stress in CS-induced vascular damage.

Main Methods:

  • Male BALB/c mice exposed to CS or room air for 8 weeks.
  • Mice treated daily with ebselen or vehicle.
  • Assessed pulmonary inflammation via bronchoalveolar lavage fluid.
  • Evaluated thoracic aorta vascular responses ex vivo.

Main Results:

  • CS exposure increased lung inflammation, reduced by ebselen.
  • CS caused endothelial dysfunction in the aorta.
  • Aortic dysfunction linked to decreased eNOS expression and increased oxidative stress.
  • Ebselen treatment reversed endothelial dysfunction by reducing oxidative stress and preserving eNOS.

Conclusions:

  • CS-induced oxidative stress contributes to vascular dysfunction.
  • Ebselen mitigates CS-induced vascular and pulmonary damage.
  • Targeting oxidative stress with ebselen may treat smoking-related cardiovascular and pulmonary diseases.