Journal
ACTA PHYSIOLOGICA
Volume 219, Issue 4, Pages 728-756Publisher
WILEY
DOI: 10.1111/apha.12749
Keywords
cyclooxygenase; endothelin; hypoxia; nitric oxide; nucleotides; pulmonary hypertension
Categories
Funding
- 'ALF' foundation
- Actelion Pharmaceuticals Sweden AB
Ask authors/readers for more resources
Hypoxic pulmonary vasoconstriction (HPV) serves to optimize ventilation-perfusion matching in focal hypoxia and thereby enhances pulmonary gas exchange. During global hypoxia, however, HPV induces general pulmonary vasoconstriction, which may lead to pulmonary hypertension (PH), impaired exercise capacity, right-heart failure and pulmonary oedema at high altitude. In chronic hypoxia, generalized HPV together with hypoxic pulmonary arterial remodelling, contribute to the development of PH. The present article reviews the principal pathways in the invivo modulation of HPV, hypoxic pulmonary arterial remodelling and PH with primary focus on the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways. In summary, endothelin-1 and thromboxane A(2) may enhance, whereas nitric oxide and prostacyclin may moderate, HPV as well as hypoxic pulmonary arterial remodelling and PH. The production of prostacyclin seems to be coupled primarily to cyclooxygenase-1 in acute hypoxia, but to cyclooxygenase-2 in chronic hypoxia. The potential role of adenine nucleotides in modulating HPV is unclear, but warrants further study. Additional modulators of the pulmonary vascular responses to hypoxia may include angiotensin II, histamine, serotonin/5-hydroxytryptamine, leukotrienes and epoxyeicosatrienoic acids. Drugs targeting these pathways may reduce acute and/or chronic hypoxic PH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors may additionally improve exercise capacity in hypoxia. Importantly, the modulation of the pulmonary vascular responses to hypoxia varies between species and individuals, with hypoxic duration and age. The review also define how drugs targeting the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways may improve pulmonary haemodynamics, but also impair pulmonary gas exchange by interference with HPV in chronic lung diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available