s<scp>GC</scp> stimulation totally reverses hypoxia‐induced pulmonary vasoconstriction alone and combined with dual endothelin‐receptor blockade in a porcine model

Lundgren, Jakob; Kylhammar, David; Hedelin, P.; Rådegran, Göran

doi:10.1111/j.1748-1716.2012.02445.x

Cited by 13 publications

(10 citation statements)

References 45 publications

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“…Hypoxia is certainly one factor involved in the pathogenesis of pulmonary hypertension in association with pulmonary fibrosis. Hypoxia-induced pulmonary vasoconstriction can be attenuated by the stimulation of soluble guanylate cyclase (Lundgren et al 2012), which is the main enzyme activated by nitric oxide and which catalyses the conversion of guanosin-5′-triphosphate into the second messenger cyclic guanosine-3′-5′-monophosphate. Pravastatin reduces the development of monocrotaline-induced pulmonary hypertension and improves endothelium-dependent pulmonary artery relaxation, in part through restoring endothelial nitric oxide synthase expression .…”

Section: Discussionmentioning

confidence: 99%

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin‐treated rats

et al. 2013

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Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

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Section: Discussionmentioning

confidence: 99%

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin‐treated rats

et al. 2013

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“…In contrast, overexpression of sGC inhibited the formation of neointima in the presence of a NO donor in balloon-injured rat carotid arteries (Laber et al 2002, Ahluwalia et al 2004. Moreover, (3-(5′-hydroxymethyl-2′furyl)-1-benzyl indazole (YC-1), the synthetic sGC activator, profoundly suppresses SMC proliferation through a cGMP pathway (Hussain et al 1999, Ahluwalia et al 2004, Lundgren et al 2012. Additionally, activation of sGC is required for NO-conferred protection from oxLDL-induced apoptosis in macrophages (Heinloth et al 2002).…”

mentioning

confidence: 84%

Activation of soluble guanylyl cyclase prevents foam cell formation and atherosclerosis

Tsou¹,

Chen²,

Zhao³

et al. 2013

Acta Physiol

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“…A stimulator of sGC also reversed HPV in pigs (Lundgren et al . ). In 4‐ to 6‐day‐old piglets with lobar atelectasis, moreover, an intravenously administered PDE5 inhibitor increased blood flow to the atelectatic lobe and impaired arterial oxygenation (Tessler et al .…”

Section: The Nitric Oxide Pathwaymentioning

confidence: 97%

The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension

Kylhammar

Rådegran

2016

Acta Physiologica

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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 in vivo 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 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.

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sGC stimulation totally reverses hypoxia‐induced pulmonary vasoconstriction alone and combined with dual endothelin‐receptor blockade in a porcine model

Cited by 13 publications

References 45 publications

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin‐treated rats

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin‐treated rats

Activation of soluble guanylyl cyclase prevents foam cell formation and atherosclerosis

The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension

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