TY - JOUR
T1 - Role of calcitonin gene-related peptide (CGRP) in chronic hypoxia-induced pulmonary hypertension in the mouse
T2 - Influence of gene transfer in vivo
AU - Bivalacqua, Trinity J.
AU - Hyman, Albert L.
AU - Kadowitz, Philip J.
AU - Paolocci, Nazareno
AU - Kass, David A.
AU - Champion, Hunter C.
N1 - Funding Information:
This work was supported in part by NIH HL16066 and HL14388, a grant from the American Heart Association-LA Affiliate, and the Arthur S. Steiner Cardiovascular Surgery Research Fund. Hunter C. Champion is a recipient of the Shin-Chun Wang Young Investigator Award of the American Physiologic Society and the Cournand and Comroe Young Investigator Award of the American Heart Association.
PY - 2002/10/15
Y1 - 2002/10/15
N2 - Calcitonin gene-related peptide (CGRP) is believed to play an important role in maintaining low pulmonary vascular resistance (PVR) and may be involved in modulating the pulmonary vascular response to chronic hypoxia. In the present study, an adenoviral vector encoding CGRP (AdRSVCGRP) was used to examine the effects of in vivo gene transfer of CGRP to the lung on increases in PVR, right ventricular mass, and pulmonary vascular remodeling that occurs in chronic hypoxia in the mouse. Following intratracheal administration of AdRSVCGRP or reporter gene mice were exposed to 16 days of chronic hypoxia (FIO2 0.10). The increase in pulmonary arterial pressure (PAP), PVR, right ventricular mass, and pulmonary vascular remodeling in response to chronic hypoxia was attenuated in animals overexpressing CGRP, whereas systemic arterial pressure was not altered. Following exposure to hypoxia, a subgroup of mice were treated with capsaicin, which did not significantly alter CGRP expression in the mouse lung. These data show that in vivo transfer of the CGRP gene to the lung attenuates the increase in PVR, right ventricular mass, and pulmonary vascular remodeling in chronically hypoxic mice with little effect on the systemic circulation. Moreover, these data suggest that adenoviral gene transfer of CGRP to the lung results in expression of the gene product in non-neural tissue.
AB - Calcitonin gene-related peptide (CGRP) is believed to play an important role in maintaining low pulmonary vascular resistance (PVR) and may be involved in modulating the pulmonary vascular response to chronic hypoxia. In the present study, an adenoviral vector encoding CGRP (AdRSVCGRP) was used to examine the effects of in vivo gene transfer of CGRP to the lung on increases in PVR, right ventricular mass, and pulmonary vascular remodeling that occurs in chronic hypoxia in the mouse. Following intratracheal administration of AdRSVCGRP or reporter gene mice were exposed to 16 days of chronic hypoxia (FIO2 0.10). The increase in pulmonary arterial pressure (PAP), PVR, right ventricular mass, and pulmonary vascular remodeling in response to chronic hypoxia was attenuated in animals overexpressing CGRP, whereas systemic arterial pressure was not altered. Following exposure to hypoxia, a subgroup of mice were treated with capsaicin, which did not significantly alter CGRP expression in the mouse lung. These data show that in vivo transfer of the CGRP gene to the lung attenuates the increase in PVR, right ventricular mass, and pulmonary vascular remodeling in chronically hypoxic mice with little effect on the systemic circulation. Moreover, these data suggest that adenoviral gene transfer of CGRP to the lung results in expression of the gene product in non-neural tissue.
KW - CGRP
KW - Pulmonary vascular bed
KW - Right ventricular hypertrophy
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U2 - 10.1016/S0167-0115(02)00100-3
DO - 10.1016/S0167-0115(02)00100-3
M3 - Article
C2 - 12220736
AN - SCOPUS:0037107393
SN - 0167-0115
VL - 108
SP - 129
EP - 133
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 2-3
ER -