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Modulation of endothelin receptors in the failing right ventricle of the heart and vasculature of the lung in human pulmonary arterial hypertension.

Kuc RE, Carlebur M, Maguire JJ, Yang P, Long L, Toshner M, Morrell NW, Davenport AP - Life Sci. (2014)

Bottom Line: In human PAH lungs, ETA receptors were significantly increased in the medial layer of small pulmonary arteries with no change detectable in MCT rat vessels.The increase in ETA receptors in arteries provides a mechanism for the beneficial vasodilator actions of ET antagonists.The increase in the ratio of ETA in RV also implicates changes to ET signalling although it is unclear if ET antagonism is beneficial but the results emphasise the unexploited potential for therapies that target the RV, to improve survival in patients with PAH.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

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Autoradiographical analysis of the density (amol/mm2) in the binding of [125I]-ET-1 to ETA and ETB to the smooth muscle (medial) of small pulmonary arteries from PAH compared to normal control lung tissues showing. There was a significant increase in ETA compared with normal vessels (A) but no change in ETB (n = 8 PAH and 7 control individuals ± s.e.mean; *p < 0.05 t-test). In the lungs of MCT rats (B), there was no change (n = 6 MCT and 6 control rats ± s.e.mean).
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f0010: Autoradiographical analysis of the density (amol/mm2) in the binding of [125I]-ET-1 to ETA and ETB to the smooth muscle (medial) of small pulmonary arteries from PAH compared to normal control lung tissues showing. There was a significant increase in ETA compared with normal vessels (A) but no change in ETB (n = 8 PAH and 7 control individuals ± s.e.mean; *p < 0.05 t-test). In the lungs of MCT rats (B), there was no change (n = 6 MCT and 6 control rats ± s.e.mean).

Mentions: Competition studies using whole cryostat sections in the lungs from patients with PAH compared to normal control tissues did not detect a significant difference in binding affinities (KD) for ETA or ETB and no change in receptor densities (BMAX) or ratio of sub-types in human PAH lungs compared with control (Fig. 2B, Table 3). In agreement, there were no changes in these parameters in MCT lungs compared with control. However, following apposition of labelled sections to radiation sensitive film, image analysis permitted the measurement of densities in discrete cell types. In the medial layer of small pulmonary arteries identified by comparison with adjacent stained sections, there was a significant increase in vascular ETA receptors in PAH compared with control small vessels (Fig. 3A, Table 3). No equivalent changes were detected in the medial layer of MCT rat lungs compared with control (Fig. 3B, Table 3).


Modulation of endothelin receptors in the failing right ventricle of the heart and vasculature of the lung in human pulmonary arterial hypertension.

Kuc RE, Carlebur M, Maguire JJ, Yang P, Long L, Toshner M, Morrell NW, Davenport AP - Life Sci. (2014)

Autoradiographical analysis of the density (amol/mm2) in the binding of [125I]-ET-1 to ETA and ETB to the smooth muscle (medial) of small pulmonary arteries from PAH compared to normal control lung tissues showing. There was a significant increase in ETA compared with normal vessels (A) but no change in ETB (n = 8 PAH and 7 control individuals ± s.e.mean; *p < 0.05 t-test). In the lungs of MCT rats (B), there was no change (n = 6 MCT and 6 control rats ± s.e.mean).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288792&req=5

f0010: Autoradiographical analysis of the density (amol/mm2) in the binding of [125I]-ET-1 to ETA and ETB to the smooth muscle (medial) of small pulmonary arteries from PAH compared to normal control lung tissues showing. There was a significant increase in ETA compared with normal vessels (A) but no change in ETB (n = 8 PAH and 7 control individuals ± s.e.mean; *p < 0.05 t-test). In the lungs of MCT rats (B), there was no change (n = 6 MCT and 6 control rats ± s.e.mean).
Mentions: Competition studies using whole cryostat sections in the lungs from patients with PAH compared to normal control tissues did not detect a significant difference in binding affinities (KD) for ETA or ETB and no change in receptor densities (BMAX) or ratio of sub-types in human PAH lungs compared with control (Fig. 2B, Table 3). In agreement, there were no changes in these parameters in MCT lungs compared with control. However, following apposition of labelled sections to radiation sensitive film, image analysis permitted the measurement of densities in discrete cell types. In the medial layer of small pulmonary arteries identified by comparison with adjacent stained sections, there was a significant increase in vascular ETA receptors in PAH compared with control small vessels (Fig. 3A, Table 3). No equivalent changes were detected in the medial layer of MCT rat lungs compared with control (Fig. 3B, Table 3).

Bottom Line: In human PAH lungs, ETA receptors were significantly increased in the medial layer of small pulmonary arteries with no change detectable in MCT rat vessels.The increase in ETA receptors in arteries provides a mechanism for the beneficial vasodilator actions of ET antagonists.The increase in the ratio of ETA in RV also implicates changes to ET signalling although it is unclear if ET antagonism is beneficial but the results emphasise the unexploited potential for therapies that target the RV, to improve survival in patients with PAH.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

Show MeSH
Related in: MedlinePlus