sGC stimulation totally reverses hypoxia-induced pulmonary vasoconstriction alone and combined with dual endothelin-receptor blockade in a porcine model.
(2012) In Acta Physiologica 206(3). p.178-194- Abstract
- AIM:
Stimulation of soluble guanylate cyclase (sGC) with BAY 41-8543 was hypothesized to attenuate acute hypoxic pulmonary vasoconstriction alone and combined with dual endothelin (ET)-receptor antagonist tezosentan.
METHODS: Measurements were taken in 18 anaesthetized pigs with a mean ± SEM weight of 31.1 ± 0.4 kg, in normoxia (FiO(2) ~0.21) and hypoxia (FiO(2) ~0.10) without (control protocol, n = 6), and with right atrial infusion of BAY 41-8543 at 1, 3, 6, 9 and 12 μg min(-1) per kg (protocol 2, n = 6) or tezosentan at 5 mg kg(-1) followed by BAY 41-8543 at 1, 3 and 6 μg min(-1) per kg (protocol 3, n = 6).
RESULTS:
Hypoxia (n = 18) increased (P < 0.001) mean pulmonary... (More) - AIM:
Stimulation of soluble guanylate cyclase (sGC) with BAY 41-8543 was hypothesized to attenuate acute hypoxic pulmonary vasoconstriction alone and combined with dual endothelin (ET)-receptor antagonist tezosentan.
METHODS: Measurements were taken in 18 anaesthetized pigs with a mean ± SEM weight of 31.1 ± 0.4 kg, in normoxia (FiO(2) ~0.21) and hypoxia (FiO(2) ~0.10) without (control protocol, n = 6), and with right atrial infusion of BAY 41-8543 at 1, 3, 6, 9 and 12 μg min(-1) per kg (protocol 2, n = 6) or tezosentan at 5 mg kg(-1) followed by BAY 41-8543 at 1, 3 and 6 μg min(-1) per kg (protocol 3, n = 6).
RESULTS:
Hypoxia (n = 18) increased (P < 0.001) mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR) by 14.2 ± 0.6 mmHg and 2.8 ± 0.3 WU respectively. During sustained hypoxia without treatment, MPAP and PVR remained stable. BAY 41-8543 (n = 6) dose-dependently decreased (P < 0.001) MPAP and PVR by 15.0 ± 1.2 mmHg and 4.7 ± 0.7 WU respectively. Tezosentan (n = 6) decreased (P < 0.001) MPAP and PVR by 11.8 ± 1.2 mmHg and 2.0 ± 0.2 WU, respectively, whereafter BAY 41-8543 (n = 6) further decreased (P < 0.001) MPAP and PVR by 6.6 ± 0.9 mmHg and 1.9 ± 0.4 WU respectively. Both BAY 41-8543 and tezosentan decreased (P < 0.001) systemic arterial pressure and systemic vascular resistance. Blood-O(2) consumption remained unaltered (P = ns) during all interventions.
CONCLUSION:
BAY 41-8543 totally reverses the effects of acute hypoxia-induced pulmonary vasoconstriction, and enhances the attenuating effects of tezosentan, without affecting oxygenation. Thus, sGC stimulation, alone or combined with dual ET-receptor blockade, could offer a means to treat pulmonary hypertension related to hypoxia and potentially other causes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2859623
- author
- Lundgren, J LU ; Kylhammar, David LU ; Hedelin, P and Rådegran, Göran LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Acta Physiologica
- volume
- 206
- issue
- 3
- pages
- 178 - 194
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000309392300004
- pmid:22682645
- scopus:84866902404
- pmid:22682645
- ISSN
- 1748-1708
- DOI
- 10.1111/j.1748-1716.2012.02445.x
- language
- English
- LU publication?
- yes
- id
- 86659260-e30d-4c18-b020-dcb08ce5c318 (old id 2859623)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22682645?dopt=Abstract
- date added to LUP
- 2016-04-04 07:12:00
- date last changed
- 2022-01-29 01:54:55
@article{86659260-e30d-4c18-b020-dcb08ce5c318,
abstract = {{AIM: <br/><br>
Stimulation of soluble guanylate cyclase (sGC) with BAY 41-8543 was hypothesized to attenuate acute hypoxic pulmonary vasoconstriction alone and combined with dual endothelin (ET)-receptor antagonist tezosentan. <br/><br>
<br/><br>
METHODS: Measurements were taken in 18 anaesthetized pigs with a mean ± SEM weight of 31.1 ± 0.4 kg, in normoxia (FiO(2) ~0.21) and hypoxia (FiO(2) ~0.10) without (control protocol, n = 6), and with right atrial infusion of BAY 41-8543 at 1, 3, 6, 9 and 12 μg min(-1) per kg (protocol 2, n = 6) or tezosentan at 5 mg kg(-1) followed by BAY 41-8543 at 1, 3 and 6 μg min(-1) per kg (protocol 3, n = 6). <br/><br>
<br/><br>
RESULTS: <br/><br>
Hypoxia (n = 18) increased (P < 0.001) mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR) by 14.2 ± 0.6 mmHg and 2.8 ± 0.3 WU respectively. During sustained hypoxia without treatment, MPAP and PVR remained stable. BAY 41-8543 (n = 6) dose-dependently decreased (P < 0.001) MPAP and PVR by 15.0 ± 1.2 mmHg and 4.7 ± 0.7 WU respectively. Tezosentan (n = 6) decreased (P < 0.001) MPAP and PVR by 11.8 ± 1.2 mmHg and 2.0 ± 0.2 WU, respectively, whereafter BAY 41-8543 (n = 6) further decreased (P < 0.001) MPAP and PVR by 6.6 ± 0.9 mmHg and 1.9 ± 0.4 WU respectively. Both BAY 41-8543 and tezosentan decreased (P < 0.001) systemic arterial pressure and systemic vascular resistance. Blood-O(2) consumption remained unaltered (P = ns) during all interventions. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
BAY 41-8543 totally reverses the effects of acute hypoxia-induced pulmonary vasoconstriction, and enhances the attenuating effects of tezosentan, without affecting oxygenation. Thus, sGC stimulation, alone or combined with dual ET-receptor blockade, could offer a means to treat pulmonary hypertension related to hypoxia and potentially other causes.}},
author = {{Lundgren, J and Kylhammar, David and Hedelin, P and Rådegran, Göran}},
issn = {{1748-1708}},
language = {{eng}},
number = {{3}},
pages = {{178--194}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Physiologica}},
title = {{sGC stimulation totally reverses hypoxia-induced pulmonary vasoconstriction alone and combined with dual endothelin-receptor blockade in a porcine model.}},
url = {{http://dx.doi.org/10.1111/j.1748-1716.2012.02445.x}},
doi = {{10.1111/j.1748-1716.2012.02445.x}},
volume = {{206}},
year = {{2012}},
}