Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries. / Hasbak, Philip; Sheykhzade, Majid; Schifter, Søren; Edvinsson, Lars.

In: Journal of Cardiovascular Pharmacology, Vol. 63, No. 1, 01.2014, p. 58-67.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hasbak, P, Sheykhzade, M, Schifter, S & Edvinsson, L 2014, 'Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries', Journal of Cardiovascular Pharmacology, vol. 63, no. 1, pp. 58-67. https://doi.org/10.1097/FJC.0000000000000025

APA

Hasbak, P., Sheykhzade, M., Schifter, S., & Edvinsson, L. (2014). Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries. Journal of Cardiovascular Pharmacology, 63(1), 58-67. https://doi.org/10.1097/FJC.0000000000000025

Vancouver

Hasbak P, Sheykhzade M, Schifter S, Edvinsson L. Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries. Journal of Cardiovascular Pharmacology. 2014 Jan;63(1):58-67. https://doi.org/10.1097/FJC.0000000000000025

Author

Hasbak, Philip ; Sheykhzade, Majid ; Schifter, Søren ; Edvinsson, Lars. / Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries. In: Journal of Cardiovascular Pharmacology. 2014 ; Vol. 63, No. 1. pp. 58-67.

Bibtex

@article{355101464f174ef7bf57ac6163c0279a,
title = "Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries",
abstract = "This study describes the effect of variable oxygen supply on relaxing responses induced by αCGRP and adrenomedullin (AM) on isolated pig coronary arteries in vitro. Organ culture during normoxia (21% O2) and hypoxia (5% O2) induced a significant leftward shift of the AM concentration-response curves compared to fresh vessels altering the pEC50 values from 6.9 ± 0.04 to 8.0 ± 0.04, whereas the potency (pEC50) of αCGRP was attenuated from 8.8 ± 0.04 to 7.6 ± 0.04. AM22-52 exerted significant antagonistic effect on AM-induced vasorelaxation in hypoxic and normoxic conditions (apparent pKB = 6.8 - 7.2), whereas no antagonistic effect was observed in fresh and hyperoxic (95 %) organ cultured vessels. The antagonistic effect exerted by αCGRP8-37 (10 - 10 M) on αCGRP-induced vasodilatation in fresh vessels (derived from Schild plot pA2 = 7.4 ± 0.1) was unaltered during organ culture. The antagonistic effect exerted by αCGRP8-37 (10M) on AM-induced vasorelaxation in fresh vessels (apparent pKB = 7.4 ± 0.1) was absent during hypoxic organ culture. TheRAMP1/Calcitonin like receptor (CLR) mRNA ratio was reduced and RAMP2/CLR mRNA ratio increased during hypoxic and normoxic organ culture compared to fresh vessels. Hypoxic organ culture for 24h - 72h potentiated the AM induced vasorelaxation via an AM22-52 sensitive receptor but attenuated the vasorelaxant effect of CGRP via the CGRP receptors. This could possibly be explained by relatively decreased levels of RAMP1, thus favoring RAMP2 + CLR complex (= AM receptor) formation during hypoxic organ culture.",
author = "Philip Hasbak and Majid Sheykhzade and S{\o}ren Schifter and Lars Edvinsson",
year = "2014",
month = jan,
doi = "10.1097/FJC.0000000000000025",
language = "English",
volume = "63",
pages = "58--67",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams & Wilkins",
number = "1",

}

RIS

TY - JOUR

T1 - Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ cultured porcine coronary arteries

AU - Hasbak, Philip

AU - Sheykhzade, Majid

AU - Schifter, Søren

AU - Edvinsson, Lars

PY - 2014/1

Y1 - 2014/1

N2 - This study describes the effect of variable oxygen supply on relaxing responses induced by αCGRP and adrenomedullin (AM) on isolated pig coronary arteries in vitro. Organ culture during normoxia (21% O2) and hypoxia (5% O2) induced a significant leftward shift of the AM concentration-response curves compared to fresh vessels altering the pEC50 values from 6.9 ± 0.04 to 8.0 ± 0.04, whereas the potency (pEC50) of αCGRP was attenuated from 8.8 ± 0.04 to 7.6 ± 0.04. AM22-52 exerted significant antagonistic effect on AM-induced vasorelaxation in hypoxic and normoxic conditions (apparent pKB = 6.8 - 7.2), whereas no antagonistic effect was observed in fresh and hyperoxic (95 %) organ cultured vessels. The antagonistic effect exerted by αCGRP8-37 (10 - 10 M) on αCGRP-induced vasodilatation in fresh vessels (derived from Schild plot pA2 = 7.4 ± 0.1) was unaltered during organ culture. The antagonistic effect exerted by αCGRP8-37 (10M) on AM-induced vasorelaxation in fresh vessels (apparent pKB = 7.4 ± 0.1) was absent during hypoxic organ culture. TheRAMP1/Calcitonin like receptor (CLR) mRNA ratio was reduced and RAMP2/CLR mRNA ratio increased during hypoxic and normoxic organ culture compared to fresh vessels. Hypoxic organ culture for 24h - 72h potentiated the AM induced vasorelaxation via an AM22-52 sensitive receptor but attenuated the vasorelaxant effect of CGRP via the CGRP receptors. This could possibly be explained by relatively decreased levels of RAMP1, thus favoring RAMP2 + CLR complex (= AM receptor) formation during hypoxic organ culture.

AB - This study describes the effect of variable oxygen supply on relaxing responses induced by αCGRP and adrenomedullin (AM) on isolated pig coronary arteries in vitro. Organ culture during normoxia (21% O2) and hypoxia (5% O2) induced a significant leftward shift of the AM concentration-response curves compared to fresh vessels altering the pEC50 values from 6.9 ± 0.04 to 8.0 ± 0.04, whereas the potency (pEC50) of αCGRP was attenuated from 8.8 ± 0.04 to 7.6 ± 0.04. AM22-52 exerted significant antagonistic effect on AM-induced vasorelaxation in hypoxic and normoxic conditions (apparent pKB = 6.8 - 7.2), whereas no antagonistic effect was observed in fresh and hyperoxic (95 %) organ cultured vessels. The antagonistic effect exerted by αCGRP8-37 (10 - 10 M) on αCGRP-induced vasodilatation in fresh vessels (derived from Schild plot pA2 = 7.4 ± 0.1) was unaltered during organ culture. The antagonistic effect exerted by αCGRP8-37 (10M) on AM-induced vasorelaxation in fresh vessels (apparent pKB = 7.4 ± 0.1) was absent during hypoxic organ culture. TheRAMP1/Calcitonin like receptor (CLR) mRNA ratio was reduced and RAMP2/CLR mRNA ratio increased during hypoxic and normoxic organ culture compared to fresh vessels. Hypoxic organ culture for 24h - 72h potentiated the AM induced vasorelaxation via an AM22-52 sensitive receptor but attenuated the vasorelaxant effect of CGRP via the CGRP receptors. This could possibly be explained by relatively decreased levels of RAMP1, thus favoring RAMP2 + CLR complex (= AM receptor) formation during hypoxic organ culture.

U2 - 10.1097/FJC.0000000000000025

DO - 10.1097/FJC.0000000000000025

M3 - Journal article

C2 - 24084221

VL - 63

SP - 58

EP - 67

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 1

ER -

ID: 92540628